Search Results (1,065)

The dried root of Sanguisorba officinalis L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells (HUVECs) and isolated phenylephrine-precontracted rat thoracic aortic rings were examined to investigate the possible mechanism of a butanol extract of Diyu (BSO) in its vascular relaxant effect. HUVECs treated with BSO produced a significantly higher amount of nitric oxide (NO) compared to the control. However, its production was inhibited by pretreatment with N^G-nitro-L-arginine methylester (L-NAME) or wortmannin. BSO also increased the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt. In the aortic ring, BSO relaxed PE-precontracted rat thoracic aortic rings in a concentration-dependent manner. The absence of the vascular endothelium significantly attenuated BSO-induced vasorelaxation. The non-selective NOS inhibitor, L-NAME, and the selective inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), dramatically inhibited the BSO-induced relaxation effect of the endothelium-intact aortic ring. Ca²⁺-free buffer and intracellular Ca²⁺ homeostasis regulators (TG, Gd³⁺, and 2–APB) inhibited BSO-induced vasorelaxation. In Ca²⁺-free Krebs solution, BSO markedly reduced PE-induced contraction. Vasodilation induced by BSO was significantly inhibited by wortmannin, an inhibitor of Akt. Pretreatment with the non-selective inhibitor of Ca²⁺-activated K⁺ channels (K_Ca), tetraethylammonium (TEA), significantly attenuated the BSO-induced vasorelaxant effect. Furthermore, BSO decreased the systolic blood pressure and heart rate in a concentration-dependent manner in rats. In conclusion, BSO induces vasorelaxation via endothelium-dependent signaling, primarily through the activation of the PI3K-Akt-eNOS-NO signaling pathway in endothelial cells, and the activation of the NO-sGC-cGMP-K⁺ channels pathway in vascular smooth muscle cells. Additionally, store-operated Ca²⁺ entry (SOCE)-eNOS pathways and the inhibition of Ca²⁺ mobilization from intracellular stores contribute to BSO-induced vasorelaxation. Full article

L-arginine, a semi-essential amino acid, is well-documented for its role in nitric oxide (NO) synthesis, its anti-inflammatory properties, and its modulation of immune responses. Studies suggest it may improve gut barrier function and reduce inflammation in conditions such as colitis or sepsis. However, its specific efficacy in diabetic enteropathy (a complication of diabetes involving intestinal dysfunction, inflammation, and neuropathy) is less studied. To verify whether L-arginine and silkworm pupae components have a role in the treatment of diabetic enteropathy via the regulation of other cytokines and suppression of CD4+ T lymphocyte proliferation, a special medical-purpose formula containing both of these components was tested. For the first time, we have integrated L-arginine and silkworm pupae protein into enteral nutrition formulations for testing its anti-inflammatory potential. We have found that these formulations can improve the characteristics of diabetic intestinal inflammation through nutrient-modulating effects and nutritional efficacy. In addition, L-arginine (L-arginine, L-arg) enhances the immunomodulatory effects of special medical purpose formulas for diabetes mellitus. We utilized an oxidative stress model of small intestinal epithelial cells induced by high glucose and an inflammation model of the small intestine triggered by lipopolysaccharide in mice. The aim was to further investigate the protective effects of L-arginine and enteral nutritional preparations derived from silkworm pupae protein components on the intestinal tract. This research seeks to establish a theoretical foundation for understanding how L-arginine and these nutritional preparations regulate intestinal inflammation in vivo. Full article

A fixed ratio amount, i.e., L-arginine (LA) and trisodium phosphate dodecahydrate (TSP) at 2:0.25, is considered as a hybrid inhibitor. This research aims to extensively investigate the impact of utilizing the hybrid corrosion inhibitor on the corrosion resistance properties in accelerated condition, mechanical characteristics, and predictive estimation of the lifespan of reinforced concrete (RC) structures. Various experiments, such as setting time, slump, air content, porosity, compressive strength, and chloride diffusion coefficient, were conducted to elucidate the influence of the hybrid corrosion inhibitor on the mechanical properties of the concrete matrix. Meanwhile, linear polarization resistance (LPR) and electrochemical impedance spectroscopy (EIS) in 10 wt. % NaCl under wet–dry cycles are utilized to assess the corrosion resistance property, corrosion initiation time, and kinetics of the passive film formation on the steel rebar. Alternatively, both deterministic and probabilistic-based predictions of service life by Life 365 software are utilized to demonstrate the efficacy of the hybrid corrosion inhibitor in protecting the steel rebar in RC structures. All the results confirm that the HI-4 mix (LA:TSP = 3.56:0.44) exhibits excellence in preventing the corrosion and extending the service life of RC structures, due to the adsorption of inhibitor molecules and formation of P-Zwitterions-(Cl)-Fe, Zwitterions-(Cl)-Fe, and FePO₄ complexes onto the steel rebar surface. However, HI-3 shows the optimal mechanical and electrochemical properties for RC structures. Full article

Background/Objectives: Identifying effective and safe treatment options for non-infectious uveitis remains challenging due to chronic and relapsing ocular inflammation. Previous studies have shown that artesunate (ART) plays an immunosuppressive role in several classic autoimmune diseases, including uveitis. However, its impact on the plasma metabolic profile of recurrent autoimmune uveitis remains unclear. This study aims to explore the effect of ART on the plasma metabolic features of recurrent experimental autoimmune uveitis (EAU) in a Lewis rat. Methods: Rats were clinically and pathologically evaluated for the development of recurrent EAU induced by inter-photoreceptor retinoid-binding protein (IRBP) R16 peptide-specific T-cells (tEAU). The disruptive effects of ART on tEAU were investigated to evaluate the potential role of rat recurrent EAU. Differentially expressed metabolites were identified in the plasma of rats by untargeted metabolomics analysis after ART treatment. The differential metabolites were applied to subsequent pathway analysis and biomarker analysis by MetaboAnalyst. Results: ART can significantly alleviate the severity of clinical signs and pathological injuries of eyeballs with tEAU. Both non-supervised principal component analysis and orthogonal partial least-squares discriminant analysis showed 84 differential metabolites enriched in 16 metabolic pathways in the tEAU group compared with heathy controls and 51 differential metabolites enriched in 17 metabolic pathways, including arginine and proline metabolism, alanine metabolism, and aminoacyl-tRNA biosynthesis, in the ART-treated group compared with the tEAU group. Particularly, upregulated L-alanine levels in both alanine metabolism and aminoacyl-tRNA biosynthesis were associated with T-cell activation, while elevated spermidine and N-acetyl putrescine levels in arginine and proline metabolism related to T-cell differentiation proved to be valuable biomarkers for ART treatment. Conclusions: Our study demonstrates that ART treatment can alleviate recurrent uveitis by altering the plasma metabolic characteristics associated with T-cell activation and differentiation, which might provide novel insights for potential therapeutic treatments. Full article

Litopenaeus vannamei is a key economic species in aquaculture, yet the molecular mechanisms underlying its growth variability remain unclear. This study conducted transcriptomic and metabolomic analyses of fast-growing (NL) and slow-growing (NS) shrimp under identical conditions. A total of 1280 differentially expressed genes (DEGs) related to protein processing, ribosomes, and oxidative phosphorylation, along with 5297 differentially abundant metabolites (DMs) involved in arginine biosynthesis, amino acid metabolism, and pantothenate and CoA biosynthesis, were identified and analyzed. An integrative analysis revealed that the NL shrimp exhibited an enhanced retinol, glutathione, riboflavin, and purine metabolism, which implies a higher tolerance to environmental stress. In contrast, the NS shrimp showed increased fatty acid degradation and an accelerated TCA cycle. This suggests that NS shrimp might require a substantial amount of energy to cope with environmental changes, consequently resulting in increased energy expenditures. This study provides significant insights into the molecular mechanisms underlying the growth disparity in L. vannamei, offering valuable data for future research aimed at optimizing shrimp growth performance and enhancing aquaculture productivity. Full article

Field pea (Pisum sativum L.) is one of the most important grain legumes in European agriculture, having many benefits for agro-ecosystems and also one of the lowest carbon footprints of any crop. However, this crop has many more drawbacks when grown organically as opposed to conventionally. Therefore, our study aims to investigate the performance of newly bred field pea varieties and to test their differences of adaptivity to organic and conventional farming systems. Our study evaluated productivity, as well as the biological and nutritional parameters of the following four new field pea varieties: Lina DS, Egle DS, Ieva DS and Jura DS, all cultivated in the Nemoral climatic zone, where field peas are widely produced. The performance was compared with the long-term standard field pea variety Ingrid. Our study showed that all investigated new varieties had higher productivity compared to the long-term standard Ingrid. The organic cropping system limited the grain yield of field pea, and different varieties tended to respond differently to this type of crop management. Therefore, different varieties should be selected and suggested for organic and conventional cropping systems. Furthermore, with various different responses to the precipitation level, different varieties could be suggested for farming in different regions. The nutritional value (content of proteins and amino acids) also responded significantly to the management system and the selection of field pea variety. Newly bred variety Egle DS demonstrated the highest grain yields, and the highest content of proteins and essential amino acids in the seeds of field pea grown in an organic farming system. Egle DS accumulated 30 percent higher content of arginine compared to the standard variety. Full article

Background/Objectives: The Canadian goldenrod (Solidago canadensis L.) is one of the most widespread species of the genus Solidago from the Asteraceae family. It has a rich composition of biologically active compounds and is traditionally used to address kidney, urinary tract, and liver diseases. Previously, it was proven that the S. canadensis extract obtained with a 40% ethanol solution had the most promising anti-inflammatory and hepatoprotective activity. Therefore, this extract was selected for the further formulation of amino acid preparations and 3D-printed dosage forms. The aims of the present study were to investigate the chemical composition, toxicity, and antimicrobial, anti-inflammatory, and hepatoprotective activity of S. canadensis dry extract, its amino acid preparations, and 3D-printed dosage forms. Results: A total of 18 phenolic compounds and 14 amino acids were determined in the extracts. The S. canadensis herb extracts were verified to be practically non-toxic preparations (toxicity class V, LD₅₀ > 5000 mg/kg). They also showed moderate antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, and β-hemolytic Streptococcus pyogenes. The most pronounced hepatoprotective activity was observed with S. canadensis herb extract and its amino acid preparations with phenylalanine, alanine, and lysine at a dose of 25 mg/kg body weight. The most pronounced anti-inflammatory activity was found with S. canadensis herb extract and its preparation with arginine. According to the calculated docking score array and the analysis of binding modes in the active sites of COX-1 and COX-2, the flavonoid fraction and caffeic acid in the S. canadensis extracts presented moderate inhibitory activity. Conclusions: The development of innovative 3D-printed oral dosage forms represents a promising strategy to formulate dietary supplements or pharmaceutical preparations for these herbal extracts. Full article

Background: The dietary supplement citrulline might increase nitric oxide levels, leading to vasodilation and improved blood flow, potentially benefiting athletes’ aerobic exercise performance. However, rapid oxidative impairment of the L-arginine/nitric oxide (NO) pathway limits these effects. This is countered by Bergamot Polyphenolic Fraction Gold^® (BPFG), a strong natural antioxidant. To investigate L-citrulline + BPFG supplementation’s effects, we performed a randomized, double-blind, placebo-controlled pilot trial on athletic performance and blood flow in trained athletes (cyclists). Methods: Random assignment of 90 male athletes resulted in nine different groups: placebo for Group 1, BPFG at 500 and 1000 mg daily for Groups 2 and 3, L-citrulline at 1000 and 2000 mg/daily for Groups 4 and 5, and the combination product of BPFG plus citrulline (N.O. Max) for Groups 6–9. Baseline and 3-month pre- and post-exercise biochemical, reactive vasodilation (RHI), and maximal oxygen consumption measurements were taken for all subjects. Results: Three months of the combination of BPFG and L-citrulline (N.O. Max) produced a significant synergistic effect, markedly increasing NO (p < 0.001 vs. placebo) release and RHI (p < 0.001 vs. placebo). Cardiorespiratory fitness improved significantly with the BPFG and L-citrulline combination, resulting in substantially higher VO₂ max, VT1, VT2, and peak power and a significantly lower heart rate (p < 0.01 vs. placebo). No harmful adverse effects were observed. Conclusions: N.O. Max supplementation, providing beneficial effects on the antioxidant state and preserving the vascular endothelium might be a supplementation strategy to improve athletic performance and potentiate results. Given the small sample size, this study serves as a pilot, and further research is needed to validate these findings on a larger scale. Full article

Chronic kidney disease (CKD) has become one of the most rapidly advancing diseases of the century, contributing significantly to increased mortality and morbidity. Metabolomics presents a promising approach to understanding CKD pathogenesis and identifying novel biomarkers for early diagnosis. This study evaluated serum and urine metabolomic profiles in CKD patients with declining glomerular filtration rates (eGFR). Using targeted metabolomics, we quantified seven potential metabolites in blood and urine samples from 20 healthy individuals and 99 CKD patients staged by eGFR according to the KDIGO guidelines. The analysis was conducted using ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. The metabolites investigated included L-phenylalanine, L-methionine, arginine, indoxyl sulfate, kynurenic acid, and L-acetylcarnitine. Quantitative assessments were performed using pure standards and validated through methods such as the limit of detection (LOD) and limit of quantification (LOQ). The findings identified potential biomarkers for early CKD diagnosis: in serum, L-phenylalanine, L-methionine, arginine, kynurenic acid, and indoxyl sulfate, while L-acetylcarnitine was significant in urine. These biomarkers could provide valuable insights into CKD progression and support in developing more effective diagnostic tools for early intervention. Full article

In recent years, there have been many studies on the response of plants to heavy metal stress, but the metabolic changes in bryophytes, pioneer plants quickly responding to environmental changes, under exogenous cadmium (Cd) stress have yet to be explored. In this indoor experiment, the responses in the metabolome of bryophyte Tortella tortuosa (Hedw.) Limpr. to different Cd exposure levels (0 (CK), 5 (T1), and 10 (T2) mg·L⁻¹) were analyzed. The results showed that the number of differentially accumulated metabolites (DAMs) secreted by T. tortuosa increased with the increase in the Cd concentration, and the biosynthesis of cofactors, D-Amino acid metabolism, Arginine biosynthesis, ATP-binding cassette transporters (ABC transporters), and biosynthesis of alkaloids derived from shikimate pathway were the main pathways enriched by DAMs. The relative abundances of malic acid, N-Formylkynurenine, L-Glutamine, L-Histidine, LL-2,6-Diaminopimelic acid, and fusaric acid in the T2 treatment increased by 16.06%, 62.51%, 14.51%, 11.92%, 21.37%, and 35.79%, respectively (p < 0.05), compared with those of the CK, and the correlation analysis results showed that the above DAMs were closely related to the changes in plant antioxidant enzyme activity and Cd concentration. These results indicate that the secretion of amino acid (N-Formylkynurenine, L-Histidine) and organic acids (isocitric acid, LL-2,6-Diaminopimelic acid, malic acid) through the metabolic pathways, including biosynthesis of amino acids, biosynthesis of cofactors, glyoxylate and dicarboxylate metabolism, and ABC transporters, is the metabolic mechanism of T. tortuosa to resist exogenous Cd stress. This study will provide a reference for the monitoring and remediation of heavy metal pollution. Full article

Drought stress significantly impairs the output of tea plants and the quality of tea products. Although Serendipita indica has demonstrated the ability to enhance drought tolerance in host plants, its impact on tea plants (Camellia sinensis) experiencing drought stress is unknown. This study assessed the response of tea plants by inoculating S. indica under drought conditions. Phenotypic and physiological analyses demonstrated that S. indica mitigated drought damage in tea plants by regulating osmotic equilibrium and antioxidant enzyme activity. Metabolome analysis showed that S. indica promoted the accumulation of flavonoid metabolites, including naringin, (-)-epiafzelechin, naringenin chalcone, and dihydromyricetin, while inhibiting the content of amino acids and derivatives, such as homoarginine, L-arginine, N6-acetyl-L-lysine, and N-palmitoylglycine, during water deficit. The expression patterns of S. indica-stimulated genes were investigated using transcriptome analysis. S. indica-induced drought-responsive genes involved in osmotic regulation, antioxidant protection, transcription factors, and signaling were identified and recognized as possibly significant in S. indica-mediated drought tolerance in tea plants. Particularly, the flavonoid biosynthesis pathway was identified from the metabolomic and transcriptomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Moreover, flavonoid biosynthesis-related genes were identified. S. indica-inoculation significantly upregulated the expression of cinnamate 4-hydroxylase (C4H), chalcone synthase (CHS), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidin reductase (ANR), and leucoanthocyanidin reductase (LAR) genes compared to uninoculated plants subjected to water stress. Consequently, we concluded that S. indica inoculation primarily alleviates drought stress in tea plants by modulating the flavonoid biosynthesis pathway. These results will provide insights into the mechanisms of S. indica-enhanced drought tolerance in tea plants and establish a solid foundation for its application as a microbial agent in the management of drought in tea plants cultivation. Full article

Cardiovascular diseases (CVDs), which include multiple disorders of the heart and blood vessels, are the leading causes of death. Nitric oxide (NO) is a vasodilator that regulates vascular tension. Endogenous NO is produced via the L-arginine–nitric oxide synthase (NOS) pathway. In conditions of cardiovascular dysfunction, NOS activity is impaired, leading to NO deficiency. In turn, the reduction in NO bioactivity exacerbates the pathogenesis of CVDs. Exogenous intake of inorganic nitrate supplements endogenous production via the nitrate–nitrite–NO pathway to maintain the NO supply. Salivary glands play an essential role in the conversion of nitrate to NO, with approximately 25% of circulating nitrate being absorbed and secreted into saliva. As a result, salivary nitrate concentrations can exceed that in the blood by more than tenfold. This recycled nitrate in saliva serves as a reservoir for NO and performs NO-like functions when endogenous NO production is insufficient. In this review, we summarize the emerging benefits of dietary nitrate in CVDs, with a particular focus on salivary-gland-mediated nitrate recirculation in maintaining NO bioavailability and cardiovascular homeostasis. Salivary-gland-mediated nitrate recirculation provides a novel perspective for potential intervention of CVDs. Full article

Acinetobacter (A.) baumannii is a major nosocomial pathogen in human and veterinary medicine. The emergence of certain international clones (ICs), often with multidrug-resistant (MDR) phenotypes and biofilm formation (BF), facilitates its spread in clinical environments. The global rise in antimicrobial resistance demands alternative treatment strategies, such as antimicrobial peptides (AMPs). In this study, 45 human and companion animal MDR-A. baumannii isolates, belonging to the globally spread IC1, IC2 and IC7, were tested for antimicrobial resistance and biofilm-associated genes (BAGs) and their capacity for BF. Of these, 13 were used to test the inhibitory effect of AMPs on bacterial growth (BG) and BF through the application of a crystal violet assay. The two novel AMP variants Bac7(17) (target cell inactivation) and Pasmr5-17 (efflux pump inhibition) and the well-known AMP phenylalanine-arginine-β-naphthylamide (PAβN) were tested at concentrations of 1.95 to 1000 µg/mL. Based on whole-genome sequence data, identical patterns of BAGs were detected within the same IC. AMPs inhibited BG and BF in a dose-dependent manner. Bac7(17) and PAsmr5-17 were highly effective against BG, with growth inhibition (GI) of >99% (62.5 and 125 µg/mL, respectively). PAβN achieved only 95.7% GI at 1000 µg/mL. Similar results were obtained for BF. Differences between the ICs were found for both GI and BF when influenced by AMPs. PAsmr5-17 had hardly any inhibitory effect on the BF of IC1 isolates, but for IC2 and IC7 isolates, 31.25 µg/mL was sufficient. Our data show that the susceptibility of animal MDR-A. baumannii to AMPs most likely resembles that of human isolates, depending on their assignment to a particular IC. Even low concentrations of AMPs had a significant effect on BG. Therefore, AMPs represent a promising alternative in the treatment of MDR-A. baumannii, either as the sole therapy or in combination with antibiotics. Full article

Heat stress has become a significant concern in animal husbandry, as it adversely affects reproductive performance, particularly sperm quality, through mechanisms that are not fully understood. This study aimed to investigate the protective effects of L-arginine against heat stress-induced sperm damage and explore its potential mechanisms through the modulation of the intestinal microbiota. This study consisted of two experiments. First, in a heat-stressed mouse model, L-arginine was administered to evaluate its effects on the reproductive health of heat-stressed mice. In the second experiment, by transplanting L-arginine-induced changes in the gut microbiota into heat-stressed mice, the protective effects of the microbiota on the sperm of heat-stressed mice were assessed. The findings revealed a significant amelioration of decreased sperm quality and testicular injury induced by heat stress. Post heat stress, mice supplemented with L-arginine presented an increase in seminal vesicle gland weight and index, partial alleviation of testicular tissue morphology, and a substantial increase in testosterone concentration (p < 0.05). Additionally, L-arginine upregulated the expression of testosterone synthesis genes and the mRNA levels of sperm generation-related genes, including 3β-HSD, Stra8, WT1, and Gdnf (p < 0.05). Concurrently, L-arginine-induced microbial communities mitigated heat stress-induced decreases in sperm quality and testicular injury, coupled with increases in the mRNA expression levels of Cyp17a1, 17β-HSD, Plzf, and Gdnf (p < 0.05). Furthermore, there was a reduction in the expression of proinflammatory factors, namely, NFκB, MyD88, TNF-α, and TGF-β3 (p < 0.05). In conclusion, L-arginine may influence the ratio of beneficial bacteria to harmful bacteria in the intestinal microbiota, thereby reducing inflammation caused by heat stress, maintaining intestinal health, and influencing the microenvironment for spermatogenesis. Full article

This study examines how different concentrations of arginine vasopressin (AVP) and its preservative chlorobutanol (ClB) impact the immune functions of human polymorphonuclear neutrophils (PMNs), which are crucial in the immune response, particularly in sepsis. Using a model to simulate the physiological, sepsis-related, and therapeutic AVP levels in plasma, we analysed how AVP and ClB affect PMN activities, including reactive oxygen species (ROS) production, NETosis, antigen expression, and migration. PMNs were isolated from whole human blood and assessed using flow cytometry and live cell imaging. The results indicated that neither AVP nor ClB significantly affected PMN viability, antigen expression, NETosis, or ROS production in response to N-Formylmethionine-leucyl-phenylalanine, or fMLP, and tumour necrosis factor alpha. In the migration assays, concentration-dependent effects were observed. At physiological AVP levels, PMN migration showed no reduction, while the sepsis-associated AVP levels initially reduced migration before returning to the baseline or even increasing. The therapeutic AVP concentrations showed similar migration to that in the controls, while high concentrations progressively inhibited migration. ClB, regardless of its concentration, enhanced PMN migration. These findings suggest that AVP during sepsis may impair PMN migration, potentially contributing to tissue damage and systemic complications. This highlights AVP’s role as a possible immune modulator in complex immune responses. Full article