In the past decade,people have conducted extensive research on the synthesis and application properties of various functionalized pillararenes.Pillararenes show good application prospects in the field of sensors due t...In the past decade,people have conducted extensive research on the synthesis and application properties of various functionalized pillararenes.Pillararenes show good application prospects in the field of sensors due to the rich host-vip recognition in their rigid electron-rich cavities.However,most reported pillararenes are functionalized by alkoxy modification,which results in poor charge transfer nature and weak fluorescence response.A π-conjugated charge-transfer system P5BN was obtained by introducing electron-donating triarylamine(Ar_(3)N)and electron-deficient triarylborane(Ar_(3)B)into pillar[5]arene skeleton,which significantly improved its luminescence behavior and was further used for fluorescence detection applications.The molecular structure showed that P5BN provided a good macrocyclic cavity to encapsulate amino acids molecules of suitable size.It was found that P5BN,as a fluorescent sensor,showed a highly sensitive and selective response to L-arginine(L-Arg),resulting in a significant enhancement of the fluorescence at 408 nm of P5BN with the lowest detection concentration being 2.21×10^(-8) mol/L.The recognition mechanism was demonstrated through experiments and DFT theoretical calculations.展开更多
We comment on an article published by Mansouri et al in the World Journal of Diabetes.L-arginine(L-Arg),a dietary supplement,is a precursor of nitric oxide,can improve cardiovascular disease,and it is important for tr...We comment on an article published by Mansouri et al in the World Journal of Diabetes.L-arginine(L-Arg),a dietary supplement,is a precursor of nitric oxide,can improve cardiovascular disease,and it is important for treating heart disease and hypertension.Previous studies have demonstrated a beneficial effect of L-Arg on diabetes.In the study by Mansouri et al,L-Arg moderately increased blood glucose levels in normal rats.However,in diabetic rats,L-Arg significantly increased lipid levels,which is different from the findings of previous studies.This study demonstrated that a safe dose of 0.5 g/kg in diabetic rats can improve the lipid profile and decrease body weight.However,high doses(1 g/kg or higher)may aggravate damage to myocardial tissue in diabetic rats by increasing blood glucose,inflammation,and oxidative stress.Therefore,this study further demonstrated that high doses of L-Arg can exacerbate myocardial injury in diabetic patients.展开更多
BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial...BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.展开更多
BACKGROUND Chronic pancreatitis is a progressive,debilitating condition with no standardized treatment.Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects...BACKGROUND Chronic pancreatitis is a progressive,debilitating condition with no standardized treatment.Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects on pancreatic acinar cells.AIM To evaluate the synergistic effects of pirfenidone and simvastatin in an L-arginineinduced chronic pancreatitis model in mice.METHODS A preclinical,7-week study was performed using a mouse model of L-arginineinduced chronic pancreatitis.The mice were divided into five groups:Normal control;model control;pirfenidone-treated;simvastatin-treated;and combinationtreated(pirfenidone+simvastatin).Treatment started in week 3 after disease induction.Mice were euthanized at weeks 4 and 7 for blood collection and tissue sampling for histological and biomarker analysis,including cytokines,oxidative stress markers,and indicators of fibrosis.RESULTS Combination therapy significantly reduced levels of tumor necrosis factor-alpha(11.10±1.57 pg/mL vs 24.30±2.00 pg/mL),interleukin-10(11.70±1.12 pg/mL vs 19.60±1.27 pg/mL),and transforming growth factor-beta 1(236.13±6.95 pg/mL vs 550.52±42.18 pg/mL)at week 7(P<0.05 vs model control).The glutathione peroxidase 1 level increased across all treatment groups,significantly in the pirfenidonetreated group(5.47±0.34 IU/mL vs 5.04±0.43 IU/mL;P<0.05).Lipid peroxidation levels decreased significantly in the combination-treated group(111.87±7.36 mmol/mL vs 192.85±0.98 mmol/mL;P<0.05).Histology revealed extensive collagen accumulation and damage to the exocrine pancreas in the model control group(vs treatment groups).Combination therapy elicited the least damage.CONCLUSION Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation,fibrosis,and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model,suggesting promise for chronic pancreatitis management.展开更多
This letter addresses the study in recent publication in the World Journal of Diabetes.The study provides valuable insights and a comprehensive analysis of the effects of L-arginine(L-Arg)supplementation on cardiac he...This letter addresses the study in recent publication in the World Journal of Diabetes.The study provides valuable insights and a comprehensive analysis of the effects of L-arginine(L-Arg)supplementation on cardiac health in diabetic rats,highlighting the potential risks associated with high doses of L-Arg.The findings suggest that while low doses of L-Arg may offer some benefits,higher doses can exacerbate myocardial injury through increased oxidative stress,in-flammation,and structural disruption.This finding challenges the prevailing point of L-Arg as a universally beneficial supplement and emphasizes the need for further research in its clinical application,particularly in diabetic patients.展开更多
BACKGROUND Mesenchymal stem cell(MSC)-based therapy may be a future treatment for myocardial infarction(MI).However,few studies have assessed the therapeutic efficacy of adipose tissue-derived MSCs(ADSCs)obtained from...BACKGROUND Mesenchymal stem cell(MSC)-based therapy may be a future treatment for myocardial infarction(MI).However,few studies have assessed the therapeutic efficacy of adipose tissue-derived MSCs(ADSCs)obtained from elderly patients in comparison to that of bone marrow-derived MSCs(BMSCs)from the same elderly patients.The metabolomics results revealed a significantly higher Larginine excretion from aged ADSCs vs BMSCs in hypoxic conditions.This was hypothesized as the possible mechanism that ADSCs showed an improved angiogenic capacity and enhanced the therapeutic effect on ischemic heart diseases.AIM To investigate the role of L-arginine in enhancing angiogenesis and cardiac protection by comparing ADSCs and BMSCs in hypoxic conditions for MI therapy.METHODS Metabolomic profiling of supernatants from ADSCs and BMSCs under hypoxic conditions were performed.Then,arginine succinate lyase(ASL)overexpression and short hairpin RNA plasmid were prepared and transfected into BMSCs.Subsequently,in vitro wound healing and Matrigel tube formation assays were used to verify the proangiogenetic effects of ADSC positive control,BMSCs,BMSCs ASL short hairpin RNA,BMSCs ASL overexpressed,and BMSC negative control on cocultured human umbilical vein endothelial cells.All sample sizes,which were determined to meet the statistical requirements and be greater than 3,were established on the basis of previously established literature standards.The protein levels of vascular endothelial growth factor(VEGF),basic fibroblast growth factor,etc.were detected.In vivo,the five types of cells were transplanted into the infarcted area of MI rat models,and the therapeutic effects of the transplanted cells were evaluated by echocardiography on cardiac function and by Masson’s staining/terminal-deoxynucleotidyl transferase mediated nick end labeling assay/immunofluorescence detection on the infarcted area.RESULTS Metabolomic analysis showed that L-arginine was increased.Using ASL gene transfection,we upregulated the production of L-arginine in aged patient-derived BMSCs in vitro,which in turn enhanced mitogen activated protein kinase and VEGF receptor 2 protein expression,VEGF and basic fibroblast growth factor secretion,and inductive angiogenesis to levels comparable to donor-matched ADSCs.After the cell transplantation in vivo,the modified BMSCs as well as ADSCs exhibited decreased apoptotic cells,enhanced vessel formation,reduced scar size,and improved cardiac function in the MI rat model.The therapeutic efficacy decreased by inhibiting L-arginine synthesis.CONCLUSION L-arginine is important for inducing therapeutic angiogenesis for ADSCs and BMSCs in hypoxic conditions.ADSCs have higher L-arginine secretion,which leads to better angiogenesis induction and cardiac protection.ADSC transplantation is a promising autologous cell therapy strategy in the context of the present aging society.展开更多
Bone marrow-derived mesenchymal stem cells(BMSCs)and adipose tissuederived mesenchymal stem cells(ADSCs),two principal subtypes of mesenchymal stem cells with multilineage regenerative potential,have emerged as promis...Bone marrow-derived mesenchymal stem cells(BMSCs)and adipose tissuederived mesenchymal stem cells(ADSCs),two principal subtypes of mesenchymal stem cells with multilineage regenerative potential,have emerged as promising therapeutic strategies for various diseases.While BMSCs and ADSCs exhibit distinct functional profiles tailored to different therapeutic applications,emerging evidence suggests that ADSCs may be a more promising approach for treating ischemic pathologies,including myocardial infarction,ischemic stroke,and peripheral artery disease,in comparison with BMSCs.However,the precise molecular mechanisms by which ADSCs enhance the therapeutic outcomes in these diseases remain poorly understood.In this editorial,we comment on the article by Li et al,which systematically compares the therapeutic efficacy of ADSCs and BMSCs derived from the same elderly patients with coronary heart disease and explores the underlying mechanism from a metabolic perspective.This study proposes that the metabolite L-arginine in ADSCs isolated from elderly patients promotes angiogenesis and protects against apoptosis in a hypoxic and ischemic microenvironment,thereby enhancing myocardial repair following infarction.These findings not only highlight the metabolic plasticity of ADSCs but also position L-arginine as a pivotal therapeutic effector in coronary heart disease.Given the novel and crucial role of L-arginine in ischemic heart diseases,further exploration of L-arginine in ADSCs(particularly those derived from elderly individuals)is essential,including its roles in angiogenesis,cell death,and the potential therapeutic implications in other ischemic pathologies.Additionally,further investigation into additional metabolites in ADSCs is warranted to enhance the therapeutic potential of ADSCs in ischemic pathologies.展开更多
The article by Mansouri et al provides a comprehensive investigation into the effects of L-arginine(L-Arg)on diabetic cardiomyopathy.The authors conclude that while a low dose(0.5 g/kg)of L-Arg improves lipid profiles...The article by Mansouri et al provides a comprehensive investigation into the effects of L-arginine(L-Arg)on diabetic cardiomyopathy.The authors conclude that while a low dose(0.5 g/kg)of L-Arg improves lipid profiles and reduces body weight,higher doses(≥1 g/kg)exacerbate oxidative stress,inflammation,and myocardial damage.In this letter,we aim to expand on the potential role of anti-inflammatory and antioxidant strategies in mitigating these adverse effects.Specifically,we focus on nuclear factor erythroid 2-related factor 2 activation and nitric oxide synthase modulation.These strategies could enhance the clinical utility of L-Arg by preserving its metabolic benefits while reducing its cardiotoxic risks.We believe this perspective will stimulate future research on L-Arg-based therapies in patients with diabetes,with an emphasis on optimizing dosage and exploring synergistic co-therapies.展开更多
Nitric oxide （NO） is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of Larginine and NnitroL arginine methyle...Nitric oxide （NO） is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of Larginine and NnitroL arginine methylester （LNAME, a nitric oxide synthase inhibitor） on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of LArg （the NO precursor）, LNAME, or 0.9% NaCI （control）, once daily for seven con secutive days. Twelve hours after the last injection, they underwent an electric shockpaired Y maze test. Twentyfour hours later, the rats＇ memory of the safe illuminated arm was tested. After that, the levels of NO and a7 nicotinic acetylcholine receptor （a7 nAChR） in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, LArgtreated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memorytesting session. In contrast, LNAMEtreated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memorytesting session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in LArgtreated rats and lower inLNAME rats, compared to controls. Similarly, （]7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in LArgtreated rats and lower in LNAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with a7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Ymaze.展开更多
To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 ...To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTSThis high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSIONBPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.展开更多
Aim L-Arginine· L-aspartate, a double salt, has been recently reported toinhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This studywas conducted to investigate its effect o...Aim L-Arginine· L-aspartate, a double salt, has been recently reported toinhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This studywas conducted to investigate its effect on FITC-PAC-1, an anti-glycoprotein IIb/IIIa monoclonalantibody binding to activated platelets, and on correlative autacoid levels in plasma or inplatelets in order to explore its potential pathway of inhibiting platelet aggregation andthrombosis. Methods Monoclonal antibody binding to activated platelets was assayed by flowcytometry; NO was assessed by colorimetric method. cAMP, TXB_2 or 6-keto-PGF_(1α) levels wereassessed by radioimmunoassay. Results Gavaged 30 mg·kg^(-1) of L-arginine·L-aspartate increasedboth concentration of NO in plasma and 6-keto-PGF_(1) in incubated supernatant of aortic segment ofrats ex vivo (P < 0.05), but it did not influence cAMP content in platelets and the level of TXB_2or 6-keto-PGF_(1) in plasma of rats, whereas ASA significantly lowered TXB_2 or 6-keto-PGF_(1α) inplasma. Both 100 μmol-L^(-1) of L-arginine ·L-aspartate and ASA inhibited FITC-PAC-1 binding toactivated platelets in vitro. Conclusion The increase in NO and PGI_2 release from endo-thelialcells and consequent inhibition of platelet activation may contribute to the inhibition of plateletaggregation and thrombosis by L-arginine· L-aspartate; whereas arachidonic acid or cAMP metabolicpathway is not closely correlative with the studied effect.展开更多
AIM： To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis （SAP） and the regulatory effect of L-arginine. METHODS： Male adult Wistar rats were randomly di...AIM： To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis （SAP） and the regulatory effect of L-arginine. METHODS： Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3＋, CD4＋, CD8＋ T lymphoo/tes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A （SIgA） in cecum feces was examined by radioimmunoassay. RESULTS： Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3＋ and CD4＋ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly, CD4＋/CD8＋ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3＋ and CD4＋ T lymphocyte percentage in the end of intestinal mucosal lamina propria, an increased ratio of CD4＋/CD8＋ and a higher SIgA concentration in cecum feces. CONCLUSION： Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.展开更多
Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate...Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate the effects of in ovo feeding(IOF)of L-arginine(Arg)on growth,intestinal development,intestinal microbiota and metabolism.The treatments included the non-injected control,saline-injected control,and saline containing 2,6,or 10 mg Arg groups.Results:IOF Arg increased early intestinal index and villus height,and enhanced uptake of residual yolk lipid,contributing to subsequent improvement in the early growth performance of chicks.Prenatal Arg supplementation also increased the early microbialα-diversity,the relative abundance of Lactobacillales and Clostridiales,and decreased the relative abundance of Proteobacteria of cecum in chicks.Furthermore,the shift of cecal microbiota composition and the colonization of potential probiotics were accelerated by IOF of Arg.Simultaneously,metabolomics showed that metabolisms of galactose,taurine-conjugated bile acids and lipids were modulated to direct more energy and nutrients towards rapid growth of intestine at the beginning of post-hatch when embryos received IOF of Arg.Conclusions:Prenatal Arg supplementation showed beneficial effects on the early intestinal development,cecal microbiota and host metabolism of layer chicks,contributing to subsequent improvement in the early growth performance.These findings provide new insight into the role of IOF of Arg in the establishment of the gut microbiota of newly-hatched layer chicks,and can expand our fundamental knowledge about prenatal nutrition,early bacterial colonization and intestinal development in neonate.展开更多
AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO a...AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO and some other cytokines change in the reperfusion period and these changes are associated with lung injury. The aim of this study was to determine the effect of supplementing NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production during small intestinal IR in immature rats. METHODS: Immature rats underwent 60 min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L-arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg) which received L-arg after 45 min of intestinal ischemia. Serum and lung endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor a (TNFα) were measured. Sham operation (SHAM) and intestinal IR (IR) groups were performed as control. The lavage fluid of the lung was collected by bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells (PMNs) were immediately counted to identify lung damage. RESULTS: When L-arg was given during small intestinal IR, serum NO concentration increased significantly in IR+L-arg group (162.17±42.93 μmol/L) when compared with IR group (87.57±23.17 μmol/L, t=3.190, P= 0.008 <0.01). Serum MDA reduced significantly in IR+L-arg group (8.93±1.50 nmol/L) when compared with SHAM (23.78±7.81 nmol/L, t= 3.243, P= 0.007<0.01) and IR (25.54±9.32 nmol/L, t= 3.421, P= 0.006<0.01). ET-1 level in lung tissues was significantly lower in IR+L-arg group (13.81±7.84 pg/mL) than that in SHAM (35.52±10.82 pg/mL, t= 2,571, P= 0,03<0.05) and IR (50.83±22.05 pg/mL, t= 3.025, P= 0.009<0.01) groups. MDA contents in lung tissues were significantly lower in IR+L-arg group (10.73±1.99 nmol/L) than in SHAM (16.62±2.28 nmol/L, t= 3.280, P = 0.007<0.01) and IR (21.90±4.82 nmol/L, t= 3.322, P= 0.007<0.01) groups. Serum and lung TNFα concentrations were not significantly different in three groups. NO contents in lung homogenates and white blood cell counts in BAL had no significant difference in three groups; but the percentage of PMNs in BAL was 13.50±8.92, 33.20±16.59, and 22.50±6.09 in SHAM, IR, and IR+L-arg groups, respectively. CONCLUSION: Small intestinal IR induced increases of pulmonary neutrophil infiltration in immature rats. Neutrophil infiltration in lung tissues was reduced by L-arg administration but remained higher than in SHAM group. L-arg administration during intestinal IR enhances serum NO production, reduces serum MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic endothelial function. L-arg supplementation before reperfusion may act as a useful clinical adjunct in the management of intestinal IR, thus preventing the development of adult respiratory distress syndrome, even multiple organ dysfunction syndrome (MODS).展开更多
文摘In the past decade,people have conducted extensive research on the synthesis and application properties of various functionalized pillararenes.Pillararenes show good application prospects in the field of sensors due to the rich host-vip recognition in their rigid electron-rich cavities.However,most reported pillararenes are functionalized by alkoxy modification,which results in poor charge transfer nature and weak fluorescence response.A π-conjugated charge-transfer system P5BN was obtained by introducing electron-donating triarylamine(Ar_(3)N)and electron-deficient triarylborane(Ar_(3)B)into pillar[5]arene skeleton,which significantly improved its luminescence behavior and was further used for fluorescence detection applications.The molecular structure showed that P5BN provided a good macrocyclic cavity to encapsulate amino acids molecules of suitable size.It was found that P5BN,as a fluorescent sensor,showed a highly sensitive and selective response to L-arginine(L-Arg),resulting in a significant enhancement of the fluorescence at 408 nm of P5BN with the lowest detection concentration being 2.21×10^(-8) mol/L.The recognition mechanism was demonstrated through experiments and DFT theoretical calculations.
基金Supported by The Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2024KY138The Basic Research Project of Wenzhou Municipal Science and Technology Bureau,No.Y20240008+1 种基金The Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)The Key Laboratory of School of Laboratory Medicine and Life Sciences,Wenzhou Medical University of China,No.JS2023003.
文摘We comment on an article published by Mansouri et al in the World Journal of Diabetes.L-arginine(L-Arg),a dietary supplement,is a precursor of nitric oxide,can improve cardiovascular disease,and it is important for treating heart disease and hypertension.Previous studies have demonstrated a beneficial effect of L-Arg on diabetes.In the study by Mansouri et al,L-Arg moderately increased blood glucose levels in normal rats.However,in diabetic rats,L-Arg significantly increased lipid levels,which is different from the findings of previous studies.This study demonstrated that a safe dose of 0.5 g/kg in diabetic rats can improve the lipid profile and decrease body weight.However,high doses(1 g/kg or higher)may aggravate damage to myocardial tissue in diabetic rats by increasing blood glucose,inflammation,and oxidative stress.Therefore,this study further demonstrated that high doses of L-Arg can exacerbate myocardial injury in diabetic patients.
基金The Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, No. IF2/PSAU/2022/03/23339.
文摘BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.
文摘BACKGROUND Chronic pancreatitis is a progressive,debilitating condition with no standardized treatment.Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects on pancreatic acinar cells.AIM To evaluate the synergistic effects of pirfenidone and simvastatin in an L-arginineinduced chronic pancreatitis model in mice.METHODS A preclinical,7-week study was performed using a mouse model of L-arginineinduced chronic pancreatitis.The mice were divided into five groups:Normal control;model control;pirfenidone-treated;simvastatin-treated;and combinationtreated(pirfenidone+simvastatin).Treatment started in week 3 after disease induction.Mice were euthanized at weeks 4 and 7 for blood collection and tissue sampling for histological and biomarker analysis,including cytokines,oxidative stress markers,and indicators of fibrosis.RESULTS Combination therapy significantly reduced levels of tumor necrosis factor-alpha(11.10±1.57 pg/mL vs 24.30±2.00 pg/mL),interleukin-10(11.70±1.12 pg/mL vs 19.60±1.27 pg/mL),and transforming growth factor-beta 1(236.13±6.95 pg/mL vs 550.52±42.18 pg/mL)at week 7(P<0.05 vs model control).The glutathione peroxidase 1 level increased across all treatment groups,significantly in the pirfenidonetreated group(5.47±0.34 IU/mL vs 5.04±0.43 IU/mL;P<0.05).Lipid peroxidation levels decreased significantly in the combination-treated group(111.87±7.36 mmol/mL vs 192.85±0.98 mmol/mL;P<0.05).Histology revealed extensive collagen accumulation and damage to the exocrine pancreas in the model control group(vs treatment groups).Combination therapy elicited the least damage.CONCLUSION Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation,fibrosis,and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model,suggesting promise for chronic pancreatitis management.
基金Supported by National Natural Science Foundation of China,No.81670747Huangshi Municipal Health Commission Key Projects,No.WJ2024006.
文摘This letter addresses the study in recent publication in the World Journal of Diabetes.The study provides valuable insights and a comprehensive analysis of the effects of L-arginine(L-Arg)supplementation on cardiac health in diabetic rats,highlighting the potential risks associated with high doses of L-Arg.The findings suggest that while low doses of L-Arg may offer some benefits,higher doses can exacerbate myocardial injury through increased oxidative stress,in-flammation,and structural disruption.This finding challenges the prevailing point of L-Arg as a universally beneficial supplement and emphasizes the need for further research in its clinical application,particularly in diabetic patients.
基金Supported by the National Natural Science Foundation of China,No.82472147the Key Research and Development Program of Heilongjiang Province of China,No.2023ZX06C04the Open Fund of Key Laboratory of Hepatosplenic Surgery,Ministry of Education,Harbin,China,No.GPKF202402.
文摘BACKGROUND Mesenchymal stem cell(MSC)-based therapy may be a future treatment for myocardial infarction(MI).However,few studies have assessed the therapeutic efficacy of adipose tissue-derived MSCs(ADSCs)obtained from elderly patients in comparison to that of bone marrow-derived MSCs(BMSCs)from the same elderly patients.The metabolomics results revealed a significantly higher Larginine excretion from aged ADSCs vs BMSCs in hypoxic conditions.This was hypothesized as the possible mechanism that ADSCs showed an improved angiogenic capacity and enhanced the therapeutic effect on ischemic heart diseases.AIM To investigate the role of L-arginine in enhancing angiogenesis and cardiac protection by comparing ADSCs and BMSCs in hypoxic conditions for MI therapy.METHODS Metabolomic profiling of supernatants from ADSCs and BMSCs under hypoxic conditions were performed.Then,arginine succinate lyase(ASL)overexpression and short hairpin RNA plasmid were prepared and transfected into BMSCs.Subsequently,in vitro wound healing and Matrigel tube formation assays were used to verify the proangiogenetic effects of ADSC positive control,BMSCs,BMSCs ASL short hairpin RNA,BMSCs ASL overexpressed,and BMSC negative control on cocultured human umbilical vein endothelial cells.All sample sizes,which were determined to meet the statistical requirements and be greater than 3,were established on the basis of previously established literature standards.The protein levels of vascular endothelial growth factor(VEGF),basic fibroblast growth factor,etc.were detected.In vivo,the five types of cells were transplanted into the infarcted area of MI rat models,and the therapeutic effects of the transplanted cells were evaluated by echocardiography on cardiac function and by Masson’s staining/terminal-deoxynucleotidyl transferase mediated nick end labeling assay/immunofluorescence detection on the infarcted area.RESULTS Metabolomic analysis showed that L-arginine was increased.Using ASL gene transfection,we upregulated the production of L-arginine in aged patient-derived BMSCs in vitro,which in turn enhanced mitogen activated protein kinase and VEGF receptor 2 protein expression,VEGF and basic fibroblast growth factor secretion,and inductive angiogenesis to levels comparable to donor-matched ADSCs.After the cell transplantation in vivo,the modified BMSCs as well as ADSCs exhibited decreased apoptotic cells,enhanced vessel formation,reduced scar size,and improved cardiac function in the MI rat model.The therapeutic efficacy decreased by inhibiting L-arginine synthesis.CONCLUSION L-arginine is important for inducing therapeutic angiogenesis for ADSCs and BMSCs in hypoxic conditions.ADSCs have higher L-arginine secretion,which leads to better angiogenesis induction and cardiac protection.ADSC transplantation is a promising autologous cell therapy strategy in the context of the present aging society.
基金Supported by National Natural Science Foundation of China,No.82303047,No.82372507,No.82172196,and No.32401046atural Science Foundation of Hunan Province,No.2022JJ40801.
文摘Bone marrow-derived mesenchymal stem cells(BMSCs)and adipose tissuederived mesenchymal stem cells(ADSCs),two principal subtypes of mesenchymal stem cells with multilineage regenerative potential,have emerged as promising therapeutic strategies for various diseases.While BMSCs and ADSCs exhibit distinct functional profiles tailored to different therapeutic applications,emerging evidence suggests that ADSCs may be a more promising approach for treating ischemic pathologies,including myocardial infarction,ischemic stroke,and peripheral artery disease,in comparison with BMSCs.However,the precise molecular mechanisms by which ADSCs enhance the therapeutic outcomes in these diseases remain poorly understood.In this editorial,we comment on the article by Li et al,which systematically compares the therapeutic efficacy of ADSCs and BMSCs derived from the same elderly patients with coronary heart disease and explores the underlying mechanism from a metabolic perspective.This study proposes that the metabolite L-arginine in ADSCs isolated from elderly patients promotes angiogenesis and protects against apoptosis in a hypoxic and ischemic microenvironment,thereby enhancing myocardial repair following infarction.These findings not only highlight the metabolic plasticity of ADSCs but also position L-arginine as a pivotal therapeutic effector in coronary heart disease.Given the novel and crucial role of L-arginine in ischemic heart diseases,further exploration of L-arginine in ADSCs(particularly those derived from elderly individuals)is essential,including its roles in angiogenesis,cell death,and the potential therapeutic implications in other ischemic pathologies.Additionally,further investigation into additional metabolites in ADSCs is warranted to enhance the therapeutic potential of ADSCs in ischemic pathologies.
文摘The article by Mansouri et al provides a comprehensive investigation into the effects of L-arginine(L-Arg)on diabetic cardiomyopathy.The authors conclude that while a low dose(0.5 g/kg)of L-Arg improves lipid profiles and reduces body weight,higher doses(≥1 g/kg)exacerbate oxidative stress,inflammation,and myocardial damage.In this letter,we aim to expand on the potential role of anti-inflammatory and antioxidant strategies in mitigating these adverse effects.Specifically,we focus on nuclear factor erythroid 2-related factor 2 activation and nitric oxide synthase modulation.These strategies could enhance the clinical utility of L-Arg by preserving its metabolic benefits while reducing its cardiotoxic risks.We believe this perspective will stimulate future research on L-Arg-based therapies in patients with diabetes,with an emphasis on optimizing dosage and exploring synergistic co-therapies.
基金supported by Undergraduate Innovational Experimentation Program of Shanxi Province, China (2009103)
文摘Nitric oxide （NO） is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of Larginine and NnitroL arginine methylester （LNAME, a nitric oxide synthase inhibitor） on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of LArg （the NO precursor）, LNAME, or 0.9% NaCI （control）, once daily for seven con secutive days. Twelve hours after the last injection, they underwent an electric shockpaired Y maze test. Twentyfour hours later, the rats＇ memory of the safe illuminated arm was tested. After that, the levels of NO and a7 nicotinic acetylcholine receptor （a7 nAChR） in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, LArgtreated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memorytesting session. In contrast, LNAMEtreated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memorytesting session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in LArgtreated rats and lower inLNAME rats, compared to controls. Similarly, （]7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in LArgtreated rats and lower in LNAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with a7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Ymaze.
文摘To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTSThis high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSIONBPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.
文摘Aim L-Arginine· L-aspartate, a double salt, has been recently reported toinhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This studywas conducted to investigate its effect on FITC-PAC-1, an anti-glycoprotein IIb/IIIa monoclonalantibody binding to activated platelets, and on correlative autacoid levels in plasma or inplatelets in order to explore its potential pathway of inhibiting platelet aggregation andthrombosis. Methods Monoclonal antibody binding to activated platelets was assayed by flowcytometry; NO was assessed by colorimetric method. cAMP, TXB_2 or 6-keto-PGF_(1α) levels wereassessed by radioimmunoassay. Results Gavaged 30 mg·kg^(-1) of L-arginine·L-aspartate increasedboth concentration of NO in plasma and 6-keto-PGF_(1) in incubated supernatant of aortic segment ofrats ex vivo (P < 0.05), but it did not influence cAMP content in platelets and the level of TXB_2or 6-keto-PGF_(1) in plasma of rats, whereas ASA significantly lowered TXB_2 or 6-keto-PGF_(1α) inplasma. Both 100 μmol-L^(-1) of L-arginine ·L-aspartate and ASA inhibited FITC-PAC-1 binding toactivated platelets in vitro. Conclusion The increase in NO and PGI_2 release from endo-thelialcells and consequent inhibition of platelet activation may contribute to the inhibition of plateletaggregation and thrombosis by L-arginine· L-aspartate; whereas arachidonic acid or cAMP metabolicpathway is not closely correlative with the studied effect.
文摘AIM： To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis （SAP） and the regulatory effect of L-arginine. METHODS： Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3＋, CD4＋, CD8＋ T lymphoo/tes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A （SIgA） in cecum feces was examined by radioimmunoassay. RESULTS： Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3＋ and CD4＋ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly, CD4＋/CD8＋ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3＋ and CD4＋ T lymphocyte percentage in the end of intestinal mucosal lamina propria, an increased ratio of CD4＋/CD8＋ and a higher SIgA concentration in cecum feces. CONCLUSION： Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.
基金This study was supported by National Key R&D Program of China(2017YFD0500500)the earmarked fund for Modern Agro-industry Technology Research System(CARS-40-K12)+1 种基金Beijing Innovation Consortium of Agriculture Research System(BAIC04–2018)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences.
文摘Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate the effects of in ovo feeding(IOF)of L-arginine(Arg)on growth,intestinal development,intestinal microbiota and metabolism.The treatments included the non-injected control,saline-injected control,and saline containing 2,6,or 10 mg Arg groups.Results:IOF Arg increased early intestinal index and villus height,and enhanced uptake of residual yolk lipid,contributing to subsequent improvement in the early growth performance of chicks.Prenatal Arg supplementation also increased the early microbialα-diversity,the relative abundance of Lactobacillales and Clostridiales,and decreased the relative abundance of Proteobacteria of cecum in chicks.Furthermore,the shift of cecal microbiota composition and the colonization of potential probiotics were accelerated by IOF of Arg.Simultaneously,metabolomics showed that metabolisms of galactose,taurine-conjugated bile acids and lipids were modulated to direct more energy and nutrients towards rapid growth of intestine at the beginning of post-hatch when embryos received IOF of Arg.Conclusions:Prenatal Arg supplementation showed beneficial effects on the early intestinal development,cecal microbiota and host metabolism of layer chicks,contributing to subsequent improvement in the early growth performance.These findings provide new insight into the role of IOF of Arg in the establishment of the gut microbiota of newly-hatched layer chicks,and can expand our fundamental knowledge about prenatal nutrition,early bacterial colonization and intestinal development in neonate.
基金Supported by The Natural Scientific Foundation of Shandong Province, No. Q99C13
文摘AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO and some other cytokines change in the reperfusion period and these changes are associated with lung injury. The aim of this study was to determine the effect of supplementing NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production during small intestinal IR in immature rats. METHODS: Immature rats underwent 60 min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L-arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg) which received L-arg after 45 min of intestinal ischemia. Serum and lung endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor a (TNFα) were measured. Sham operation (SHAM) and intestinal IR (IR) groups were performed as control. The lavage fluid of the lung was collected by bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells (PMNs) were immediately counted to identify lung damage. RESULTS: When L-arg was given during small intestinal IR, serum NO concentration increased significantly in IR+L-arg group (162.17±42.93 μmol/L) when compared with IR group (87.57±23.17 μmol/L, t=3.190, P= 0.008 <0.01). Serum MDA reduced significantly in IR+L-arg group (8.93±1.50 nmol/L) when compared with SHAM (23.78±7.81 nmol/L, t= 3.243, P= 0.007<0.01) and IR (25.54±9.32 nmol/L, t= 3.421, P= 0.006<0.01). ET-1 level in lung tissues was significantly lower in IR+L-arg group (13.81±7.84 pg/mL) than that in SHAM (35.52±10.82 pg/mL, t= 2,571, P= 0,03<0.05) and IR (50.83±22.05 pg/mL, t= 3.025, P= 0.009<0.01) groups. MDA contents in lung tissues were significantly lower in IR+L-arg group (10.73±1.99 nmol/L) than in SHAM (16.62±2.28 nmol/L, t= 3.280, P = 0.007<0.01) and IR (21.90±4.82 nmol/L, t= 3.322, P= 0.007<0.01) groups. Serum and lung TNFα concentrations were not significantly different in three groups. NO contents in lung homogenates and white blood cell counts in BAL had no significant difference in three groups; but the percentage of PMNs in BAL was 13.50±8.92, 33.20±16.59, and 22.50±6.09 in SHAM, IR, and IR+L-arg groups, respectively. CONCLUSION: Small intestinal IR induced increases of pulmonary neutrophil infiltration in immature rats. Neutrophil infiltration in lung tissues was reduced by L-arg administration but remained higher than in SHAM group. L-arg administration during intestinal IR enhances serum NO production, reduces serum MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic endothelial function. L-arg supplementation before reperfusion may act as a useful clinical adjunct in the management of intestinal IR, thus preventing the development of adult respiratory distress syndrome, even multiple organ dysfunction syndrome (MODS).
