Effects of canagliflozin on amino acid metabolism in atherosclerotic mice / 中华心血管病杂志

Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

Effects of canagliflozin on amino acid metabolism in atherosclerotic mice / 中华心血管病杂志

Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

The relationship between reduced choroidal thickness due to high plasma asymmetrical dimethylarginine level and increased severity of diabetic retinopathy / Altos níveis de dimetil-arginina assimétrica no plasma podem aumentar a gravidade da retinopatia diabética através da redução da espessura da coroide

ABSTRACT Purpose: To evaluate the relationship between subfoveal choroidal thickness and plasma asymmetrical dimethylarginine level and the severity of diabetic retinopathy in patients with type 2 diabetes mellitus. Methods: A total of 68 cases, including 15 patients without diabetic retinopathy, 17 patients with nonproliferative diabetic retinopathy, 16 patients with type 2 diabetes mellitus and proliferative diabetic retinopathy, and 20 healthy patients (control group), were enrolled in this study. Subfoveal choroidal thickness was measured manually using the enhanced depth imaging optical coherence tomography scanning program, and plasma asymmetrical dimethylarginine level was measured using a commercial micro enzyme-linked immunosorbent assay kit. Results: The subfoveal choroidal thickness values and plasma asymmetrical dimethylarginine levels were significantly different between the four groups (p<0.001 and p<0.001). The subfoveal choroidal thickness values were significantly lower in the proliferative diabetic retinopathy group than in the other three groups (no diabetic retinopathy, nonproliferative diabetic retinopathy, and control groups; p<0.001, p=0.045, and p<0.001, respectively). The plasma asymmetrical dimethylarginine levels were significantly higher in the proliferative diabetic retinopathy group than in the other three groups (p<0.001, p<0.04, and p<0.001, respectively). In addition, a significant negative correlation was also found between plasma asymmetrical dimethylarginine level and subfoveal choroidal thickness (p<0.001, r=-0.479). Conclusion: Asymmetrical dimethylarginine is an important marker of endothelial dysfunction and endogenous endothelial nitric oxide synthase inhibitor. The severity of diabetic retinopathy was related to increased plasma asymmetrical dimethylarginine level and reduced subfoveal choroidal thickness in type 2 diabetic patients with diabetic retinopathy.

RESUMO Objetivo: Avaliar a relação da espessura subfoveal da coroide e dos níveis plasmáticos de dimetil-arginina assimétrica com a gravidade da retinopatia diabética em pacientes com diabetes mellitus tipo 2. Métodos: Foram incluídos 68 casos, compreendendo 15 pacientes sem retinopatia diabética, 17 pacientes com retinopatia diabética não proliferativa, 16 pacientes com retinopatia diabética proliferativa, e 20 casos saudáveis (grupo de controle). A espessura subfoveal da coroide foi medida manualmente, usando o programa de varredura com tomografia computadorizada óptica com imagem profunda aprimorada, e os níveis plasmáticos de dimetil-arginina assimétrica foram medidos usando um kit microELISA comercial. Resultados: Os valores da espessura subfoveal da coroide e os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente diferentes nos quatro grupos (p<0,001 para ambos os parâmetros). Os valores da espessura subfoveal da coroide foram significativamente menores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (sem retinopatia diabética, retinopatia diabética não proliferativa e grupo de controle, com p<0,001, p=0,045 e p<0,001, respectivamente). Já os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente maiores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (p<0,001, p=0,04 e p<0,001, respectivamente). Além disso, também foi encontrada uma correlação negativa significativa entre os níveis plasmáticos de dimetil-arginina assimétrica e a espessura subfoveal da coroide (p<0,001, r=-0,479). Conclusão: A dimetil-arginina assimétrica é um importante marcador de disfunção endotelial e um inibidor endógeno da óxido nítrico sintase. Foi encontrada uma relação da gravidade da retinopatia diabética e de níveis elevados de dimetil-arginina assimétrica no plasma com a redução da espessura subfoveal da coroide em pacientes diabéticos tipo 2 com retinopatia diabética.

Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology / 中国中药杂志

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

The mechanism of microcystin leucine-arginine (MC-LR)-induced injury of Sertoli cell immune response and biological behavior / 细胞与分子免疫学杂志

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.

Treatment and management for children with urea cycle disorder in chronic stage / 浙江大学学报·医学版

Urea cycle disorder (UCD) is a group of inherited metabolic diseases with high disability or fatality rate, which need long-term drug treatment and diet management. Except those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; supplementing essential amino acids and protein-free milk are also needed if necessary. The drugs for long-term use include nitrogen scavengers (sodium benzoate, sodium phenylbutyrate, glycerol phenylbutyrate), urea cycle activation/substrate supplementation agents (N-carbamylglutamate, arginine, citrulline), etc. Liver transplantation is recommended for pediatric patients not responding to standard diet and drug treatment, and those with severe progressive liver disease and/or recurrent metabolic decompensations. Gene therapy, stem cell therapy, enzyme therapy and other novel technologies may offer options for treatment in UCD patients. The regular biochemical assessments like blood ammonia, liver function and plasma amino acid profile are needed, and physical growth, intellectual development, nutritional intake should be also evaluated for adjusting treatment in time.

Is arginine supplementation effective in preventing preeclampsia in pregnant women / A suplementação de arginina é efetiva em prevenir pré-eclâmpsia em gestantes?

Objectives: The objective of this study was to review data from randomized controlled trials to assess whether or not the supplementation of L-Arginine (L-Arg) is effective in reducing the incidence of preeclampsia (PE) in pregnancies at risk of developing the disorder. Methods: We aimed to systematic review randomized controlled trials, including those which compared L-Arg supplementation with placebo in pregnant women at high risk of PE development, analyzing PE incidence as the main outcome. Data were collected from MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS and Cochrane. Results: A total of 46 papers were identified in the primary search. After analysis of eligibility, inclusion and exclusion criteria, two articles (which respected in detail all the stages of evaluation) were included in the present review. A risk of bias assessment was performed. Data analysis revealed that the incidence of PE was significantly lower in both studies, and no major adverse effects were reported. The limitations of this study were the lack of standardization between the trials analyzed and the relative low number of studies included. Conclusions: The supplementation with L-Arg appears to reduce the incidence of PE in pregnant women with high risk for its developmen (AU)

Objetivo: O objetivo deste estudo foi revisar dados de ensaios clínicos randomizados para avaliar se a suplementação de L-Arginina é efetiva para reduzir a incidência de pré-eclâmpsia em gestantes com alto risco de desenvolver a doença. Métodos: Realizamos uma revisão sistemática de ensaios clínicos randomizados, incluindo aqueles que compararam a suplementação de L-Arginina com placebo em gestantes de alto risco de desenvolvimento de pré-eclâmpsia, analisando a incidência de pré-eclâmpsia como desfecho principal. Os estudos foram selecionados do MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS e Cochrane. Resultados: Um total de 46 estudos foram identificados na busca primária. Após análise da elegibilidade, dos critérios de inclusão e de exclusão, dois artigos (que respeitaram em detalhes todas etapas de avaliação) foram incluídos na presente revisão. Foi realizada uma avaliação de risco de viés. A análise dos dados revelou que a incidência de pré-eclâmpsia foi significativamente menor em ambos os estudos, e nenhum efeito adverso importante foi relatado. As limitações deste estudo foram a falta de padronização entre os ensaios clínicos analisados e o número relativamente baixo de estudos incluídos. Conclusão: A suplementação com L-Arginina parece reduzir a incidência de pré-eclâmpsia em gestantes de alto risco para seu desenvolvimento (AU)

Is arginine supplementation effective in preventing preeclampsia in pregnant women? / A suplementação de arginina é efetiva em prevenir pré-eclâmpsia em gestantes?

ABSTRACT: Objectives: The objective of this study was to review data from randomized controlled trials to assess whether or not the supplementation of L-Arginine (L-Arg) is effective in reducing the incidence of preeclampsia (PE) in pregnancies at risk of developing the disorder. Methods: We aimed to systematic review randomized controlled trials, including those which compared L-Arg supplementation with placebo in pregnant women at high risk of PE development, analyzing PE incidence as the main outcome. Data were collected from MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS and Cochrane. Results: A total of 46 papers were identified in the primary search. After analysis of eligibility, inclusion and exclusion criteria, two articles (which respected in detail all the stages of evaluation) were included in the present review. A risk of bias assessment was performed. Data analysis revealed that the incidence of PE was significantly lower in both studies, and no major adverse effects were reported. The limitations of this study were the lack of standardization between the trials analyzed and the relative low number of studies included. Conclusions: The supplementation with L-Arg appears to reduce the incidence of PE in pregnant women with high risk for its development. (AU)

RESUMO: Objetivo: O objetivo deste estudo foi revisar dados de ensaios clínicos randomizados para avaliar se a suplementação de L-Arginina é efetiva para reduzir a incidência de pré-eclâmpsia em gestantes com alto risco de desenvolver a doença. Métodos: Realizamos uma revisão sistemática de ensaios clínicos randomizados, incluindo aqueles que compararam a suplementação de L-Arginina com placebo em gestantes de alto risco de desenvolvimento de pré-eclâmpsia, analisando a incidência de pré-eclâmpsia como desfecho principal. Os estudos foram selecionados do MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS e Cochrane. Resultados: Um total de 46 estudos foram identificados na busca primária. Após análise da elegibilidade, dos critérios de inclusão e de exclusão, dois artigos (que respeitaram em detalhes todas etapas de avaliação) foram incluídos na presente revisão. Foi realizada uma avaliação de risco de viés. A análise dos dados revelou que a incidência de pré-eclâmpsia foi significativamente menor em ambos os estudos, e nenhum efeito adverso importante foi relatado. As limitações deste estudo foram a falta de padronização entre os ensaios clínicos analisados e o número relativamente baixo de estudos incluídos. Conclusão: A suplementação com L-Arginina parece reduzir a incidência de pré-eclâmpsia em gestantes de alto risco para seu desenvolvimento. (AU)

Research progress in ecological prevention of dental caries / 中华口腔医学杂志

Dental caries is one of the most common oral diseases around the world. Dental plaque attached to the surfaces of teeth is the main biological factor leading to caries. Although fluoride is still one of the most commonly used methods to prevent caries, with the change of epidemiological characteristics of caries and the update of the understanding of caries etiology, it is necessary to use other ecological methods such as antimicrobial peptides, arginine, probiotics and natural products, etc. to enhance the effect of fluoride in preventing dental caries. The present article reviews the research progress on the ecological approaches for caries prevention in recent years.

Mechanism of emodin in relieving neuropathic pain by regulating serum metabolism / 中国中药杂志

The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery. Mechanical withdrawal threshold(MWT) and thermal withdrawal threshold(TWL) in each group were performed before the CCI surgery and 3,7, 11, and 15 days after surgery. After 15 days, blood samples were collected from the abdominal aorta. The differential metabolites were screened out by non-target metabolomics and analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG) and ingenuity pathway analysis(IPA). From the third day after CCI surgery, the MWT and TWL values were reduced significantly in both CCI group and emodin group, compared with the sham group(P<0.01). At 15 days post-surgery, the MWT and TWL values in emodin group increased significantly compared with the CCI group(P<0.05). As revealed by non-target metabolomics, 72 differential serum metabolites were screened out from the C-S comparison, including 41 up-regulated and 31 down-regulated ones, while 26 differential serum metabolites from E-C comparison, including 10 up-regulated and 16 down-regulated ones. KEGG analysis showed that the differential metabolites in E-C comparison were enriched in the signaling pathways, such as sphingolipid metabolism, arginine biosynthesis, glycerophospholipid metabolism, and tryptophan metabolism. IPA showed that the differential metabolites were mainly involved in the lipid metabolism-molecular transport-small molecule biochemistry network. In conclusion, emodin can exert an analgesic role via regulating sphingolipid metabolism and arginine biosynthesis.

Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn / 中国当代儿科杂志

OBJECTIVES@#To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response.@*METHODS@#A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA).@*RESULTS@#For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg.@*CONCLUSIONS@#There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.

Efecto simbiótico de la L-arginina más Lactobacillus rhamnosus GG sobre el crecimiento Streptcoccus mutans cariogénico en personas con desgaste dental por el consumo de gaseosas / Symbiotic effect of L-arginine plus Lactobacillus rhamnosus GG on the growth of cariogenic Streptcoccus mutans in people with dental wear due to the consumption of soft drinks

La alta prevalencia de desgaste dental erosivo producido por la ingestión frecuente de bebidas gaseosas, se ha convertido en uno de los principales problemas de salud bucal en niños, adolescentes y adultos jóvenes, cuyo tratamiento deviene en desafío para los profesionales de la salud. La investigación se propuso evaluar el efecto erosivo exógeno de las bebidas gaseosas, sobre el tejido dentario mediante el proceso de termociclado in vitro, en el que se sometieron 50 premolares extraídos a la experiencia de exposición a una bebida gaseosa, bajo condiciones de experimentación, resultando una diferencia significativa entre el peso inicial pre termociclado en cada pieza y el peso final obtenido después del proceso, lo cual demuestra el efecto negativo del consumo de bebidas gaseosas. En ese mismo sentido, y como parte de esta investigación, se evaluó los efectos beneficiosos de los probióticos como la L-alanina como suplemento de las bacterias beneficiosas a la salud bucal como el Lactobalilos rhamnosus GG que logran detener el avance de bacterias patógenas y oportunistas como el Streptococcus mutans. Los resultados mostraron que a medida que aumenta la concentración del probiótico, mayor es la disminución del número de unidades formadoras de colonias y de las biopelículas de Streptococcus mutans. Además, la investigación aborda la percepción del riesgo en estudiantes, de ingestión de bebidas gaseosas en la erosión dentaria y los criterios que sobre el tema tienen sus profesores tutores(AU)

The high prevalence of erosive dental wear caused by the frequent ingestion of soft drinks has become one of the main oral health problems in children, adolescents and young adults, whose treatment becomes a challenge for health professionals. The research aimed to evaluate the exogenous erosive effect of soft drinks on dental tissue through the in vitro thermocycling process, in which 50 extracted premolars were subjected to the experience of exposure to a soft drink, under experimental conditions, resulting in a significant difference between the initial pre-thermocycling weight in each piece and the final weight obtained after the process, which demonstrates the negative effect of the consumption of soft drinks. In that same sense, and as part of this research, the beneficial effects of probiotics such as L-alanine were evaluated as a supplement for beneficial bacteria for oral health such as Lactobalilos rhamnosus GG, which manage to stop the advance of pathogenic and opportunistic bacteria such as Streptococcus mutans. The results showed that as the concentration of the probiotic increases, the decrease in the number of colony-forming units and biofilms of Streptococcus mutans is greater. In addition, the research addresses the perception of risk in students, of ingestion of soft drinks in dental erosion and the criteria that their tutor teachers have on the subject(AU)

Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

Copper sulfate and arginine supplements on performance, thyroid hormones and blood biochemistry of broilers fed with canola meal-based diets / Avaliação da suplementação com sulfato de cobre e arginina sobre o desempenho, hormônios tireoidianos e bioquímica sanguínea de frangos alimentados com dietas à base de canola

The present evaluated the effects of copper sulfate solution (CSS) and arginine powder (Arg) supplements on performance, thyroid hormones and blood biochemistry of broiler chickens fed with canola meal (CM)-based diets. The experimental design was completely randomized with a 3 × 3 factorial and 9 treatments, corresponding to 3 levels of CSS (0, 125 and 250 mg/kg) and 3 levels of Arg (0, 0.1 and 0.2%) (n = 45 per treatment). Feeds were offered ad libitum for 21 days, from 22 to 42 days of age. Feed efficiency was significantly affected by the dietary addition of 250 mg/kg CSS and 0.2% Arg, and by the CSS × Arg interaction. CM supplemented with CSS improved the thyroid gland status and increased the plasma levels of triiodothyronine and thyroxine. Birds fed diets supplemented with 0.2% Arg had lower blood glucose level than the other treatments. The addition of 250 mg/kg CSS and 0.2% Arg reduced the stress caused by the rapid growth of broilers, also increasing the overall bird welfare.

O objetivo do presente trabalho foi avaliar os efeitos da suplementação com solução de sulfato de cobre (SSC) e arginina em pó (Arg) sobre o desempenho, hormônios tireoidianos e bioquímica sanguínea de frangos de corte alimentados com dietas à base de canola DC. O desenho experimental foi completamente casualizado com fatorial 3 × 3 e nove tratamentos correspondentes a três níveis de inclusão de SSC (0, 125 e 250 mg/kg) e três níveis de Arg (0, 0,1 e 0,2%) (n = 45 para cada tratamento). As rações foram oferecidas ad libitum por 21 dias, de 22 até 42 dias de idade. A eficiência alimentar foi significativamente afetada pela adição de 250 mg/kg de SSC e 0,2% de Arg, assim como pela interação SSC × Arg. A suplementação da DC com SSC melhorou os parâmetros da glândula tireoide e aumentou os níveis plasmáticos de triiodotironina e tiroxina. As aves alimentadas com dietas suplementadas com 0,2% de Arg apresentaram menor nível de glicose sanguínea do que as dos demais tratamentos. A adição de 250 mg/kg de SSC e 0,2% de Arg reduz o estresse causado pelo rápido crescimento dos frangos, além de melhorar as condições gerais de bem estar das aves.

Evaluación del Efecto de un Gel con Arginina sobre el PH y Flujo Salival / Evaluation of the Effect of Arginine Gel on pH and Salivary Flow

Se evaluó el efecto de un gel con arginina sobre el pH y flujo salival después de un uso de catorce días en mujeres con desmineralización dental leve. Se estableció un piloto de ensayo clínico controladoen el cual fueron incluidas 20 mujeres de 18 -23 años, sistémicamente sanas y con al menos un órgano dental con desmineralización ICDAS 3, dos grupos: Grupo A / sin arginina (N=10) y Grupo B/ con arginina (N=10). Se realizó una evaluación clínica y toma de una muestra de saliva no estimulada para la determinación del pH, y la medición del flujo salival al inicio y 15 días posterior a la utilización del gel. Se realizó el análisis estadístico con el programa GraphPadPrism versión 8. Una p<0,05 fue considerado como estadísticamente significativo. En ambos grupos se mantuvo el pH salival cercano a la neutralidad sin diferencias estadísticamente significativas y el flujo salival permaneció en valores normales tras la utilización del gel durante 14 días, aunque se observaron diferencias estadísticas significativas en la comparación inter-grupo. La utilización de un gel con arginina durante 14 días mantuvo el pH neutro y el flujo salival en niveles normales sin diferencias estadísticamente significativas con el grupo control.

The effect of an arginine gel on pH and salivary flow was evaluated after fourteen days of use in women with mild demineralization. A controlled pilot clinical trial was established in which 20 women aged 18-23 years, systemically healthy and with at least one dental organ with demineralization ICDAS 3 were included, two groups: Group A / without arginine (N = 10) and Group B / with arginine (N = 10). A clinical evaluation was carried out, and a sample of unstimulated saliva was taken to determine the pH and the measurement of salivary flow at the beginning and 15 days after using the gel. Statistical analysis was performed with the GraphPad Prism version 8 program. A p <0.05 was considered statistically significant. In both groups, salivary pH was maintained close to neutrality without statistically significant differences, and salivary flow remained at normal values after using the hydrogel for 14 days, although statistically significant differences were observed in the intergroup comparison. Using a gel with arginine for 14 days kept the neutral pH and salivary flow at normal levels without statistically significant differences from the control group.

Do the Different Types of Pulmonary Hypertension Cause the Same Effect on Right Heart and Serum Asymmetrical Dimethylarginine Levels in Female Patients?

ABSTRACT Objective: Right-heart function is a major determinant of clinical outcome in patients with elevated pulmonary artery pressure due to pulmonary venous hypertension (PVH) and pulmonary arterial hypertension (PAH). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. This study aimed to evaluate if different types of pulmonary hypertension (PH) would cause the same effect on right-heart functions and serum ADMA levels in female patients. Methods: This study included patients with PAH as group I, patients with PVH due to mitral stenosis (mitral valve area ≤ 1.5 cm2, without any additional valve or left-heart disease and systolic pulmonary artery pressure ≥ 50 mmHg in transthoracic echocardiography) as group II, and healthy control subjects as group III. Transthorasic echocardiographic evaluations for right-heart functions were performed according to the guidelines of the American Society of Echocardiography. Venous blood samples were collected, and the serum ADMA concentrations were obtained with the ELISA kit (DRG® International Inc., Springfield, NJ, USA). Results: Patients in groups I and II had higher ADMA levels than healthy control subjects. Right-atrium area and dimensions, right-ventricular (RV) volumes, grade of tricuspid regurgitation, systolic pulmonary arterial pressure, RV wall thickness, and RV outflow tract diameters were significantly higher in group I patients than in group II patients. Right-ventricular myocardial performance index was lower, and RV fractional area change and tricuspid valve systolic tissue Doppler velocity were higher in group II patients than in group I patients. Conclusion: This study demonstrated that both PAH and PVH caused increase in right-heart dimensions and impairment in right-heart functions.

Suppression of L-arginine-induced acute necrotizing pancreatitis in rats by metformin associated with the inhibition of myeloperoxidase and activation of interleukin-10 / Supresión de la pancreatitis necrotizante aguda inducida por L-arginina en ratas por metformina asociada con la inhibición de mieloperoxidasa y activación de interleucina-10

SUMMARY: Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreatitis in an animal model of L-arginine-induced acute pancreatitis, and whether this is associated with the augmentation of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibition of the enzyme that promotes tissue damage, myeloperoxidase (MPO). Rats were either injected with two doses of the amino acid L-arginine (2.5 gm/kg; i.p., at one-hour intervals) before being sacrificed after 48 hours (model group) or were pretreated with metformin (50 mg/kg) daily for two weeks prior to L- arginine injections and continued receiving metformin until the end of the experiment (protective group). Using microscopic examination of the pancreas and blood chemistry, we observed that L-arginine induced acute pancreatic injury. This is demonstrated by an enlarged pancreas with patchy areas of haemorrhage, vacuolated cytoplasm and pyknotic nuclei in the acini, disorganized lobular architecture with infiltration of inflammatory cells within the interlobular connective tissue (CT) septa, and the presence of congested blood vessels that were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited L-arginine-induced MPO, lactate dehydrogenase (LDH), and the inflammatory biomarker tumor necrosis factor alpha (TNF-α). Whereas, metformin significantly (p<0.05) increased IL-10 levels that were inhibited by pancreatitis induction. We further demonstrated a significant (p<0.001) correlation between the scoring of the degree of pancreatic lobules damage tissue damage and the blood levels of TNF-α, IL-10, LDH, and MPO. Thus, metformin effectively protects against L-arginine-induced acute pancreatitis, which is associated with the inhibition of MPO and augmentation of IL-10.

RESUMEN: La pancreatitis aguda es una enfermedad inflamatoria del páncreas que amenaza la vida y se caracteriza por un dolor abdominal intenso que dura de días a semanas. Buscamos determinar si la metformina, fármaco antidiabético y antiinflamatorio, puede proteger contra la pancreatitis aguda en un modelo animal de pancreatitis aguda inducida por L-arginina. Además se estudió la asociación con el aumento de la citocina antiinflamatoria interleucina-10. (IL-10) e inhibición de la enzima que promueve el daño tisular, mieloperoxidasa (MPO). Las ratas se inyectaron con dos dosis del aminoácido L-arginina (2,5 g / kg; ip, a intervalos de una hora) antes de ser sacrificadas des- pués de 48 horas (grupo modelo) o se pre trataron con metformina (50 mg / kg) durante dos semanas antes del tratamiento de L- arginina y continuaron recibiendo metformina hasta el final del experimento (grupo protector). Mediante el examen microscópico del páncreas y la química sanguínea, se observó que la L- arginina inducía una lesión pancreática aguda. Se observó un aumento significativo de tamaño del páncreas con áreas hemorrágicas, citoplasma vacuolado y núcleos picnóticos en los acinos, arquitectura desorganizada con infiltración de células inflamatorias dentro de los tabiques del tejido conjuntivo interlobulillar (TC) y la presencia de vasos sanguíneos congestionados mejorados por metformina. Se observó que la metformina inhibió significativamente (p <0,05) la MPO inducida por L- arginina, la lactato deshidrogenasa (LDH) y el factor de necrosis tumoral alfa (TNF-α). Además, demostramos una correlación significativa (p <0,001) entre la puntuación del grado de daño tisular de los lóbulos pancreáticos y los niveles sanguíneos de TNF-α, IL-10, LDH y MPO. Por tanto, la metformina protege eficazmente contra la pancreatitis aguda inducida por L-arginina, que se asocia con la inhibición de MPO y el aumento de IL-10.

Therapeutic effect of gene silencing peptidyl arginine deaminase 4 on pulmonary interstitial lesions induced by collagen-induced arthritis mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the therapeutic effect of gene silencing peptidyl arginine deaminase 4 (PAD4) on pulmonary interstitial lesions induced by collagen-induced arthritis (CIA) mice, and possible mechanisms.@*METHODS@#A CIA mouse model was established in DBA/1 mice, followed by a tail vein injection of the virus solution prepared by the PAD4-siRNA expression vector once a week for 8 times. The mice were sacrificed at the end of the experiment. The expression of PAD4 mRNA in lungs was detected by real-time quantitative PCR (qRT-PCR). The expression of PAD4 protein was detected by tissue immunohistochemistry. Cell culture was performed by spleen tissue. Flow cytometry changes in the ratio of Tfh cells to Tfr cells were examined; lung staining was performed in the lungs to observe changes in lung pathology.@*RESULTS@#(1) Compared with the blank group, the expression of PAD4 mRNA in the lung tissue of the model group increased, the difference was statistically significant (P < 0.05). PAD4 mRNA in the lung tissue of the CIA mice after PAD4-siRNA treatment. The expression level was significantly lower than that of the model group and the negative control group, and the difference was statistically significant (P < 0.05). (2) Red fluorescence was less in the lung tissue of the blank group, while more red fluorescence was observed in the inflammatory cell infiltration area and trachea around the lung tissue of the model group and the negative control group, and the red fluorescence of the three groups after PAD4-siRNA treatment was significantly reduced; (3) Compared with the blank group, the proportion of Tfh cells in the model group increased, the difference was statistically significant (P < 0.05), the proportion of Tfh cells in spleen cells of the CIA mice after PAD4-siRNA treatment was significantly lower than that of the model group and the negative control group, the difference was statistically significant (P < 0.05); compared with the blank group, in the mouse spleen cells in the model group the proportion of Tfr cells was slightly decreased, but the difference was not statistically signifi-cant. The proportion of Tfr cells in the spleen cells of the mice increased after PAD4-siRNA treatment, but the difference was statistically significant only in the PAD4-siRNA2 group compared with the model group and the negative control group (P < 0.05); (4) The proportion of Tfh/Tfr in the spleen cells of the model group was increased, compared with the blank group, the difference was statistically significant (P < 0.05); the ratio of Tfh/Tfr in the three groups after PAD4-siRNA treatment all decreased, the difference was statistically significant (P < 0.05); (5) Compared with the blank group, the alveolar wall of the lung tissue of the model group was thickened, the inflammatory cell infiltration was increased, and the lung tissue destruction and inflammatory infiltration of the CIA mice were decreased after PAD4-siRNA treatment. The degree of reduction was reduced.@*CONCLUSION@#Gene silencing of PAD4 can reduce the proportion of Tfh cells, increase the proportion of Tfr cells, reverse the proportion of Tfh/Tfr, and reduce the degree of interstitial lesions and inflammatory infiltration of lung tissue.

The effect of nitric oxide, endothelial nitric oxide synthetase, and asymmetric dimethylarginine in hemorrhoidal disease

SUMMARY AIM The aim of this study was to examine the roles of nitric oxide (NOx), endothelial nitric oxide synthetase (eNOS), and asymmetric dimethylarginine (ADMA), which is the major endogenous inhibitor of nitric oxide synthases (NOS), in the pathophysiology of hemorrhoidal disease. METHODS This study included 54 patients with grades 3 and 4 internal hemorrhoidal disease and 54 patients without the disease who attended the General Surgery Clinic. NOx, eNOS, and ADMA levels were measured with the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. RESULTS The patients had higher NO and eNOS levels and lower ADMA levels than the control subjects (p<0.001). A significant highly positive correlation was found between NO and eNOS (p<0.001). Nevertheless, there was a highly negative correlation between ADMA and NO-eNOS(p<0.001, p<0.001). CONCLUSION This preliminary study reveals that higher NOx and eNOS activities and lower ADMA levels in the rectal mucosa are observed in patients with hemorrhoidal disease than in those with normal rectal tissue. The imbalance between endothelium-derived relaxing factors, such as NO and endogenous competitive inhibitor of NOS, ADMA, may cause hemorrhoidal disease. Our study proposes that hemorrhoids display apparent vascular dilatation and present with bleeding or swelling. ADMA is an effective NOS inhibitor and may be a promising therapeutic option for hemorrhoidal disease.

RESUMO OBJETIVO O objetivo deste estudo foi examinar os papéis do óxido nítrico (NOx), do óxido nítrico sintetase endotelial (eNOS) e da dimetilarginina assimétrica (ADMA), que é o principal inibidor endógeno das óxido nítrico sintase (NOS) na fisiopatologia da doença hemorróida. MÉTODOS Este estudo incluiu 54 pacientes com doença hemorróida interna de grau 3 e 4 e 54 pacientes sem a doença que se inscreveram na Clínica Geral de Cirurgia. Os níveis de NOx, eNOS e ADMA foram medidos com o método de Ensaio Imuno absorvente ligado a enzima (ELISA). RESULTADOS Os pacientes têm níveis mais altos de NO e eNOS e níveis mais baixos de ADMA do que os indivíduos controle (p <0,001). Uma correlação altamente positiva significativa foi encontrada entre o NO-eNOS (p <0,001). No entanto, houve uma correlação negativa muito séria entre ADMA e NO-eNOS (p <0,001, p <0,001). CONCLUSÃO Este estudo preliminar revela que os pacientes com doença hemorróida têm atividades mais altas de NOx e eNOS e níveis mais baixos de ADMA na mucosa retal do que os pacientes com tecido retal normal. Desequilíbrio entre o fator relaxante derivado do endotélio, como; O NO e o inibidor competitivo endógeno da NOS, ADMA, podem causar doenças hemorróidas. Nosso estudo propõe que as hemorróidas exibam aparente dilatação vascular e apresentam sangramento ou inchaço, a ADMA é um inibidor eficaz da NOS e pode ser uma opção terapêutica promissora para a doença hemorróida.