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This study investigates the effect of daily consumption of wheat biscuits enriched with plant proteins in postprandial metabolic responses of women with overweight/obesity who follow an energy-restricted diet. Thirty apparently healthy women participated in a 12-week randomized controlled trial and were assigned either to a control (CB) or an intervention (PB) group. Participants consumed daily either a conventional (CB) or an isocaloric wheat biscuit enriched with plant proteins (PB) containing high amounts of amino acids with appetite-regulating properties, i.e., BCAAs and L-arg. At baseline and the end of the intervention, a mixed meal tolerance test was performed. The responses of glucose, insulin, ghrelin, GLP-1, and glicentin were evaluated over 180 min. After 12 weeks, both groups experienced significant decreases in body weight, fat mass, and waist circumference. In the PB group, a trend towards higher weight loss was observed, accompanied by lower carbohydrate, fat, and energy intakes (p < 0.05 compared to baseline and CB group), while decreases in fasting insulin and the HOMA-IR index were also observed (p < 0.05 compared to baseline). In both groups, similar postprandial glucose, ghrelin, and GLP-1 responses were detected, while iAUC for insulin was lower (p < 0.05). Interestingly, the iAUC of glicentin was greater in the PB group (p < 0.05 compared to baseline). Subjective appetite ratings were beneficially affected in both groups (p < 0.05). Consumption of wheat biscuits enriched in plant proteins contributed to greater weight loss, lower energy intake, and insulin resistance and had a positive impact on postprandial glicentin response, a peptide that can potentially predict long-term weight loss and decreased food intake. [ABSTRACT FROM AUTHOR]

L-Arg is a nonessential amino acid but has many physiological roles. Accordingly, L-Arg has been used in various fields, but there is only limited information available about its safety upon overdose. Generally, the no-observed adverse effect level (NOAEL) is used when setting the upper amount for chemical substances. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of them. Therefore, we conducted an assessment of the safety of the oral intake of L-Arg in healthy subjects using gastrointestinal symptoms as an index. We limited the study design to only double-blind randomized controlled trials and searched PubMed, Cochrane Library, EBSCOhost, and Ichushi-Web from inception until May 2021. Assessment of the quality of studies was conducted using the Cochrane Collaboration tool and Jadad score, and the random effects model was used for data analysis. Ultimately, 34 studies were selected for inclusion in this work. The dosage of L-Arg used in the studies ranged from 2000 to 30,000 mg/day (or/one-time dose), and the treatment duration was 1–84 days. The increased risk of gastrointestinal symptoms associated with L-Arg intake from 23 studies (647 participants in total) in which such symptoms were reported was 0.01 (95% confidence interval: – 0.02–0.04), which was not significant difference. NOAEL was estimated as 7531 mg/ one-time dose using a weighted change-point regression model (UMIN000046133). Registration and protocol: Umin.ac.jp as UMIN000046133. [ABSTRACT FROM AUTHOR]

Photo-immunotherapy is a promising strategy for the treatment of malignancies; however, its efficacy is often limited by the low tumor immunogenicity and immunosuppressive tumor microenvironment (TME). TME is typically deficient in L-arginine (L-Arg), which negatively impacts T cell survival and function. To address this issue, we developed a novel drug delivery system based on the multi-vesicular liposomes (MVLs) loaded with photosensitizer indocyanine green (ICG) and L-Arg (R), named R-ICG@MVLs. Under near-infrared (NIR) light irradiation, the PDT-mediated cascade reaction of reactive oxygen species (ROS) could oxidize a portion of L-Arg to generate NO, thereby inducing immunogenic tumor cell death (ITCD) and stimulating anti-tumor immune responses, including antigen-presenting cells (APCs) recruitment and T cells activation. Subsequently, R-ICG@MVLs continued to release L-Arg, which improved the immunosuppressive TME, providing nutritional support for the tumor-infiltrating T cells and thus enhancing their anti-tumor efficacy. Additionally, the photo-thermal effect of ICG could accelerate the membrane rearrangement of R-ICG@MVLs and produce multiple drug-loaded nanovesicles, thus enabling the NIR-controlled accelerated drug release. The formation of drug-loaded nanovesicles led to deeper penetration and widened the range of ICD and TME improvement, achieving a "shrapnel effect". In conclusion, our strategy realized the dual effects of immune activation and nutrition support, which might provide a clinically applicable reference for tumor immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

L-arginine (L-Arg) is a semi-essential amino acid with many important physiological functions. However, achieving efficient manufacture of L-Arg on an industrial scale using Escherichia coli (E. coli) remains a major challenge. In previous studies, we constructed a strain of E. coli A7, which had good L-Arg production capacity. In this study, E. coli A7 was further modified, and E. coli A21 with more efficient L-Arg production capacity was obtained. Firstly, we reduced the acetate accumulation of strain A7 by weakening the poxB gene and overexpressing acs gene. Secondly, we improved the L-Arg transport efficiency of strains by overexpressing the lysE gene from Corynebacterium glutamicum (C. glutamicum). Finally, we enhanced the supplies of precursors for the synthesis of L-Arg and optimized the supplies of cofactor NADPH and energy ATP in strain. After fermentation in a 5-L bioreactor, the L-Arg titer of strain A21 was found to be 89.7 g/L. The productivity was 1.495 g/(L·h) and the glucose yield was 0.377 g/g. Our study further narrowed the titer gap between E. coli and C. glutamicum in the synthesis of L-Arg. In all recent studies on the L-Arg production by E. coli, this was the highest titer recorded. In conclusion, our study further promotes the efficient mass synthesis of L-Arg by E. coli. Key points: • The acetate accumulation of starting strain A7 was decreased. • Overexpression of gene lysE of C. glutamicum enhanced L-Arg transport in strain A10. • Enhance the supplies of precursors for the synthesis of L-Arg and optimize the supplies of cofactor NADPH and energy ATP. Finally, Strain A21 was detected to have an L-Arg titer of 89.7 g/L in a 5-L bioreactor. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic ischemia reperfusion injury (IRI) takes place through liver transplantation. Hepatic IRI might seriously affect liver function and is reported to be accountable for 15 % of organ failure and could result in multi-organ dysfunction syndrome (MODS) that lead to high rates of morbidity and mortality. L-arginine (L-Arg) could reduce hepatic IRI via different mechanisms Objective: To estimate the effect of hepatic ischemic reperfusion (I/R) and the possible protective effect of L-Arg. on the adrenal cortex. Materials and Methods: Thirty two albino rats were utilized in the current work. The animals split to Sham-Operation, L-Arg, ischemic reperfusion, I/R group and I/R and L-Arg group. Then, at the assigned time, blood samples were assembled for biochemical study. Histological and immunohistochemical studies were performed on the adrenal tissue. Results: The adrenal cortex of I/R group exhibited architecture loss of the three zones. Zona glomerulosa cells showed small pyknotic nuclei and vacuolated cytoplasm. Zona fasciculata cells appeared ballooned with small pyknotic nuclei. Also, karyolitic nuclei were seen. zona reticularis cells showed pyknotic nuclei and vacuolated cytoplasm and separated by congested blood sinusoids. Hyaline material depositions were seen. Biochemical study revealed a marked increase in serum levels of liver enzymes, excess in the MDA level and a marked reduction in the CAT level compared to control group. These changes were ameliorated by L-Arg. Conclusion: Hepatic I/R has been proved to induce histological changes of the adrenal cortex which could be ameliorated by administration of L-Arg. Therefore, For inhibiting or reducing hepatic IRI through liver surgery, an effective method is urgently required. [ABSTRACT FROM AUTHOR]

As a semi-essential amino acid, l-arginine (l-Arg) plays an important role in food, health care, and medical treatment. At present, the main method of producing l-Arg is the use of microbial fermentation. Therefore, the selection and breeding of high-efficiency microbial strains is the top priority. To continuously improve the l-Arg production performance of the strains, a series of metabolic engineering strategies have been tried to transform the strains. The production of l-Arg by metabolically engineered Corynebacterium glutamicum (C. glutamicum) reached a relatively high level. Escherichia coli (E. coli), as a strain with great potential for l-Arg production, also has a large number of research strategies aimed at screening effective E. coli for producing l-Arg. E. coli also has a number of advantages over C. glutamicum in producing l-Arg. Therefore, it is of great significance to screen out excellent and stable E. coli to produce l-Arg. Here, based on recent research results, we review the metabolic pathways of l-Arg production in E. coli, the research progress of l-Arg production in E. coli, and various regulatory strategies implemented in E. coli. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a prevailing event in hypertensive patients and in frail older adults. Endothelial dysfunction has been shown to underlie both hypertension and cognitive dysfunction. Our hypothesis is that L-Arginine, which is known to ameliorate endothelial dysfunction, could counteract cognitive impairment in a high-risk population of hypertensive frail older adults. We designed a clinical trial to verify the effects of 4-weeks oral supplementation of L-Arginine on global cognitive function of hypertensive frail older patients. The study was successfully completed by 35 frail hypertensive elderly patients assigned to L-Arginine and 37 assigned to placebo. At follow-up, we found a significant difference in the Montreal Cognitive Assessment (MoCA) test score between the L-Arginine treated group and placebo (p: 0.0178). Moreover, we demonstrated that L-Arginine significantly attenuates Angiotensin II-induced mitochondrial oxidative stress in human endothelial cells. In conclusion, our findings indicate for the first time that oral L-Arginine supplementation significantly improves cognitive impairment in frail hypertensive older adults.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04962841.

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A novel AIE supramolecular polymer (BPK) was synthesized by bis(2-hydroxy-1-naphthaldehyde) terephthalo hydrazone functionalized pillar [5]arene and cross-linked using a bis(4.4-dipyridinium salt)cross-linker via host-guest complexation. BPK exhibited strong aggregation-induced emission (AIE) in binary solutions of DMSO/H 2 O. BPK could be an AIE-based sensor with specific fluorescence sensing ability for L-Arg in water. The detection limit of BPK for L-Arg was 3.95 × 10−7 M, and other amino acids did not interfere with the sensing process. Moreover, in a pure DMSO solvent, BPK can self-assemble into a fibrous structure of the right-hand spiral by guest-induced supramolecular helices. At 80 % water content, BPK undergoes a morphological transformation into supramolecular polymer. Intriguingly, BPK exhibits a reversible transformation from a polymer to a nanosphere through the alternating addition of trifluoroacetic acid and arginine. Additionally, the fluorescence of BPK demonstrates an "on-off" switch. This phenomenon is attributed to the formation and disruption of intermolecular hydrogen bonds. The reversible manipulation of polymer materials' morphology and optical properties holds significant potential in biomedicine and smart materials. An efficient guest-induced supramolecular helix was developed for the simultaneous detection of amino acids and precise morphology control by amino acids. [Display omitted] • In this study, a novel AIE supramolecular polymer was constructed by host-guest interaction. • We have constructed a highly sensitive sensing platform for arginine through multi-hydrogen bonding interactions. • We have achieved precise modulation of the morphology of supramolecular polymers by alternating adding L-Arg and TFA. • We report a novel supramolecular helical structure that can be realized by adding a guest K to the host BP. [ABSTRACT FROM AUTHOR]

A novel supramolecular fluorescent sensor (FAS) provides a synergistic effect to efficiently bind l -Arg by collaborating with the tetra-acylhyhydrazone and biphenol groups through multiple intermolecular hydrogen bonds and electrostatic attractions. [Display omitted] • A novel fluorescent sensor FAS for detection (l -Arg). • Tetra-acylhydrazone-biphenol structure provided a synergistic effect for sensing l -Arg. • The FAS shows single selectivity and high sensitivity detection for l -Arg. • Theoretical calculations provided deeply understanding of the sensing mechanism. • The method was successfully applied in the determination l -Arg in serum sample. Since l -arginine (l -Arg) is crucial to the biological system, it is important to detect l -Arg effectively. Here, we created and synthesized a brand-new fluorescence sensor (FAS) to detect l -Arg with greater sensitivity. Four acylhyhydrazone functionalized arms and two hydroxyl groups have been logically added to the FAS to increase the selectivity and sensitivity of the l -Arg sensor. These groups work together to provide effective l -Arg binding. The findings demonstrated that the FAS could specifically bind l -Arg by collaborating with the tetra-acylhyhydrazone and two hydroxyl groups through multiple intermolecular hydrogen bonds and electrostatic attractions; the sensitivity of the FAS to detect l -Arg is high, with a detection limit of 2.73 × 10−8 mol/L. Theoretical calculations and tests were used to study the potential recognition process. Furthermore, the chemosensor FAS was effectively used to ascertain the l -Arg concentration in human blood samples, indicating its capability to identify l -Arg in diverse biological matrices. [ABSTRACT FROM AUTHOR]

Context: Broiler meat with excessive of fat and saturated fatty acids content has serious health implication for consumers. The accumulation of abdominal fats in broiler chickens constitutes a loss of dietary energy and also reduces carcass yield. Oil rich in unsaturated fatty acids and l-arginine are effective for reducing fat deposition and improve meat quality. Aims: The aim of this study was to examine the effects of supplementation of l-arginine (l-Arg) with four combinations of palm oil (PO) and sunflower oil (SO) on growth performance, carcass yield, fat deposition, lipogenic gene expression and blood lipid profile in broiler chickens. Methods: A total of 180 1-day-old chicks (Cobb 500) were randomly assigned to five dietary treatments as: T1, 6% PO (control); T2, 6% PO + 0.25% l-Arg; T3, 4% PO + 2% SO + 0.25% l-Arg; T4, 2% PO + 4% SO + 0.25% l-Arg; and T5, 6% SO + 0.25% l-Arg. Key results: Birds fed l-Arg and combinations of PO and SO had higher weight gain at starter and finisher period compared with the control. The carcass yield increased, and relative abdominal fat reduced in broiler fed with combinations of l-Arg and increased level of SO in the diet. The concentration of oleic, palmitoleic and total monounsaturated fatty acids in liver tissue decreased by addition of l-Arg in broiler diet. The palmitic and total saturated fatty acid decreased, and total unsaturated fatty acid and polyunsaturated fatty acids increased in liver tissue when PO replaced progressively by SO supplemented with l-Arg in the diet. The acetyl-CoA carboxylase , stearoyl-CoA desaturase and fatty acid synthetase gene expression tended to decrease by supplementation of l-Arg with an increased level of SO compared with control. Conclusion: Supplementation with l-Arg and combination of PO and SO at the ratio of 4 : 2 could inhibit lipogenesis and subsequent lower abdominal fat deposition and enhance growth performance and carcass yield in broiler chickens. Implications: Ratio of PO and SO, 4 : 2 with l-Arg supplementation in the dietary of broiler chickens can contribute to a better growth performance, lesser fat deposition and greater carcass yield. Modern broilers have a high ability for excess fat accumulation due to genetic selections which decreases carcass yield and affects consumer acceptance of broiler meat for health-conscious issue. Supplementation with L-arginine and combination of different oil sources that rich in polyunsaturated fatty acids are effective for improving weight gain, reducing abdominal fat deposition and improve meat production in broiler chickens. [ABSTRACT FROM AUTHOR]

l-Arginine (L-Arg) depletion has attracted great attention in cancer therapy. Although two types of arginine-depleting enzymes, arginine deiminase (ADI) and human arginase I, are undergoing clinical trials, random site of PEGylation, low efficacy of heavy metal as co-factor, and immunogenicity limit the performance of these drugs and cause difficulty in a homogeneous production. Here we screened ten catalytic metal ions and have successfully produced a site-specific mono-PEGylated human arginase I mutant by conjugating the Cys45 residue to PEG-maleimide to minimize the decrease in activity and produce a homogeneous product. The catalytic efficiency trend of metal ion–enriched human arginase I mutant (HAI) was Co2+ > Ni2+ ≫ Mn2+. The overall kcat/KM values of Co-HAI and Ni-HAI were higher than Mn-HAI by ~ 8.7- and ~ 5.2-folds, respectively. Moreover, the results of enzyme kinetics and circular dichroism spectrometry demonstrated that the 20 or 40 kDa linear and branched PEG attached on the HAI surface did not affect the enzyme activity and the protein secondary structures. In vitro studies showed that both Co-HAI-PEG20L and Ni-HAI-PEG20L inhibited the growth of eight types of cancer cell lines. The pharmacodynamic study in mice demonstrated that the i.p. administration of Co-HAI-PEG20L at 13 mg/kg and Ni-HAI-PEG20L at 15 mg/kg was able to maintain a L-Arg level below its detection limit for over 120 h after one injection. The body weights of mice could return to normal levels within 5 days after injection, showing that the doses were well-tolerated. Therefore, both the Ni-HAI-PEG20L and Co-HAI-PEG20L are promising candidates for cancer therapy. Key Points: • Mono-PEGylation applied on human arginase I mutant (HAI) successfully. • The catalytic efficiency of Co- and Ni-enriched HAI was higher than the wild type. • At least eight types of cancer cell lines were inhibited by Co- and Ni-HAI-PEG20L. • Co- and Ni-HAI-PEG20L were able to achieve weekly depletion of L-Arg. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Jilin University (Science Edition) / Jilin Daxue Xuebao (Lixue Ban) is the property of Zhongguo Xue shu qi Kan (Guang Pan Ban) Dian zi Za zhi She and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Prataculturae Sinica is the property of Acta Prataculturae Sinica Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract The increased apoptosis plays an important role in bacterial invasion. In addition, LPS can induce inflammation and apoptosis of leukocytes via the production of reactive oxygen and nitrogen species. In the present study, we investigated the potential protective role of l -arginine (L-Arg) against the apoptosis of fish leukocytes in vitro. The results of Annexin V-FITC/PI staining and TUNEL assay indicated that L-Arg significantly alleviated the apoptosis of fish leukocytes induced by LPS at 24 h and 72 h post incubation (hpi). High caspase-3 activities induced by LPS at 72 hpi were significantly inhibited by L-Arg. Moreover, L-Arg supplementation also significantly decreased the mRNA expression levels of caspases at most time points, which contributed to the anti-apoptotic roles of L-Arg. Further analysis showed that L-Arg significantly inhibited the expression of several pro-inflammatory cytokines including IL-8 and TNF-α , partially via the down-regulation of the genes involved in NF-κB/MyD88 including NF-κB, IKKα and IKKγ. The down-regulation of these pro-inflammatory cytokines by L-Arg supplementation led to the further decrease in the expression of death receptor FasL, contributing to the anti-apoptotic effect of L-Arg. In addition, L-Arg supplementation increased both iNOS mRNA expression and NO production. The mRNA expressions of several anti-oxidant enzymes including SOD, CAT and GSHPx were also significantly increased after L-Arg supplementation, which accelerated the clearance of reactive oxygen species. In all, L-Arg inhibited apoptosis of fish leukocytes both via the increased NO production and antioxidant capacity and via the inhibition of inflammation mediated by NF-κB/MyD88 pathway. Highlights • l -arginine inhibited apoptosis of fish leukocytes. • l -arginine decreased inflammation via NF-κB pathway to inhibit apoptosis. • l -arginine increased NO synthesis and anti-oxidant capacity against LPS challenge. [ABSTRACT FROM AUTHOR]

Testicular dysfunction and infertility are serious complications of diabetes mellitus (DM). L -Arginine (L -Arg) is a semi essential amino acid with various biological and metabolic functions. The molecular mechanisms of L -Arg on testicular dysfunction caused by DM remain elusive. This study aimed to assess the potential protective effect of L -Arg in diabetic testis and its possible mechanisms. 24 adult male Wistar albino rats were randomly divided into four groups: CON, L -Arg that received 1 g/kg body weight of L -Arg orally for 4 weeks, DM that fed a high fat diet followed by an injection of 30 mg/kg streptozotocin intraperitoneally, and L -Arg-treated DM that were diabetic and administered L -Arg. DM decreased relative testicular weight, reduced serum testosterone, and impaired semen parameters. Reduced total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), in addition to increased transforming growth factor B1 (TGF-β1) and nitric oxide (NO) levels, were found in the testicular tissue. This was associated with severe degenerative changes in the seminiferous tubules and interstitial cells of Leydig, reduction of Johnsen's score, significantly increased expression of both inducible nitric oxide synthase (iNOS) and caspase-3, and reduced zonula occludens (ZO)− 1 expression. Ultrastructurally, disrupted intercellular junctions and degeneration of interstitial cells of Leydig were observed. In contrast, treatment of diabetic animals with L -Arg increased TAC, SOD and GSH-Px, decreased TGF-β1 and NO levels, downregulated iNOS and caspase-3 expression, upregulated ZO-1 expression, and maintained the integrity of the Sertoli cell junctions. Hence, L -Arg restored the normal testicular structure and function via its antioxidant, antiapoptotic, and antifibrotic effects. [Display omitted] • L -Arg exerted gonadoprotective effects on testicular dysfunction in diabetic rats. • L -Arg ameliorated the oxidative stress, apoptosis, and fibrosis in the testicular tissue. • L -Arg restored the normal testicular morphological structure and functions. • L -Arg maintained the integrity of the Sertoli cell junctions. [ABSTRACT FROM AUTHOR]

One-pot synthesis of N -CDs was applied as a highly efficient "ON-OFF-ON" fluorescent probe for the rapid detection of CAL and l -Arg/ l -Lys in living cells. As a consequence, these N -CDs as a powerful analysis tool displayed more prominent and influential ability in real-time monitoring CAL and l -Arg/ l -Lys, and might offer a new opportunity for exploring the physiological and pathological processes of amino acid metabolism diseases. [Display omitted] • The nitrogen-doped carbon dots (N -CDs) were synthesized via a simple one-step hydrothermal method. • These CDs could rapidly and selectively detect CAL and l -Arg/ l -Lys with the detection limits as low as 58 nM, 18 nM/16 nM, respectively. • The N -CDs as a fluorescent probe displayed low toxicity and were suitable for sensing CAL and l -Arg/ l -Lys in living cells. The disorder of amino acid metabolism and the abuse of small molecule drugs pose serious threats to public health. However, due to the limitations of existing detection technologies in sensing cinnamaldehyde (CAL) and l -Arginine/ l -Lysine (l -Arg/ l -Lys), there is an urgent need to develop new sensing strategies to meet the severe challenges currently facing. Herein, nitrogen-doped carbon dots (N -CDs) were developed using a simple one-pot hydrothermal carbonization method. These N -CDs exhibited numerous distinctive characteristics such as excellent photoluminescence, high water dispersibility, favorable biocompatibility, and superior chemical inertness. Strikingly, the as-prepared CDs as a highly efficient fluorescent probe possessed significant sensitivity and selectivity toward CAL and l -Arg/ l -Lys over other analytes with a low detection limit of 58 nM and 16 nM/18 nM, respectively. The fluorescence of N -CDs could be quenched by CAL through an electron transfer process. Then, the strong electrostatic interaction between l -Arg/ l -Lys and N -CDs induced the efficient fluorescence recovery. More importantly, the outstanding biosafety and excellent analyte-responsive fluorescence characteristics of N -CDs have also been verified in living cells as well as in serum and urine. Overall, the N -CDs had a wide application prospect in the diagnosis of amino acid metabolic diseases and small molecule drug sensing. [ABSTRACT FROM AUTHOR]

As a semi-essential amino acid, l-arginine (l-Arg) plays an important role in food, health care, and medical treatment. At present, the main method of producing l-Arg is the use of microbial fermentation. Therefore, the selection and breeding of high-efficiency microbial strains is the top priority. To continuously improve the l-Arg production performance of the strains, a series of metabolic engineering strategies have been tried to transform the strains. The production of l-Arg by metabolically engineered Corynebacterium glutamicum (C. glutamicum) reached a relatively high level. Escherichia coli (E. coli), as a strain with great potential for l-Arg production, also has a large number of research strategies aimed at screening effective E. coli for producing l-Arg. E. coli also has a number of advantages over C. glutamicum in producing l-Arg. Therefore, it is of great significance to screen out excellent and stable E. coli to produce l-Arg. Here, based on recent research results, we review the metabolic pathways of l-Arg production in E. coli, the research progress of l-Arg production in E. coli, and various regulatory strategies implemented in E. coli., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Objective: Gene therapy with viral vectors encoding for NOS enzymes has been recognized as a potential therapeutic approach for the prevention of restenosis. Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we investigated the effects of separate and combined L-Arg and BH4 supplementation on the production of NO and ROS in cultured rat arterial smooth muscle and endothelial cells transduced with AdiNOS, and their impact on the antirestenotic effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. Methods and results: Supplementation of AdiNOS transduced endothelial and vascular smooth muscle cells with L-Arg (3.0 mM), BH4 (10 μM) and especially their combination resulted in a significant increase in NO production as measured by nitrite formation in media. Formation of ROS was dose-dependently increased following transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered to meshes via a hydrolyzable cross-linker, modeling viral delivery from stents, resulted in increased ROS production, which was decreased by supplementation with BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS transduction, was also preventable with BH4 supplementation. In the rat carotid model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and especially in BH4 and L-Arg supplemented animals was found to significantly enhance the antirestenotic effects of AdiNOS-mediated gene therapy. Conclusions: Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. [Copyright &y& Elsevier]

Abstract: The interaction between l-Arg and calf thymus DNA (ctDNA) in sodium acetate–acetic acid buffer (pH=4) was investigated with the use of neutral red (NR) dye as a spectral probe coupled with UV–vis absorption, fluorescence, and circular dichroism (CD) spectroscopy technique. The UV absorption spectroscopy indicated that l-Arg interacted with ctDNA via electrostatic force and the fluorescence enhancing of the DNA–NR system verified the electrostatic interaction. In addition, detectable changes in the CD spectrum of ctDNA in the presence of l-Arg indicated conformational changes in the DNA double helix after interaction with the drug. Docking studies were found to corroborate the experimental results. All these results prove that this drug interacts with ctDNA via an electrostatic binding mode. [Copyright &y& Elsevier]

Abstract: Background/aims: Both histamine and nitric oxide (NO) may play a role in anxiety-like behavior. Within the brain, the amygdala is an important area involved in processing emotional responses such as anxiety. The aim of the present study was to assess whether the NO system in the basolateral amygdala (BLA) influences histamine-induced anxiety-like behavior in rats. Methods: Male Wistar rats weighing 200–220g were used. Bilateral cannulae were implanted in the BLA place for microinjections of drugs and the elevated plus maze apparatus has been used to test parameters (%OAT, %OAE, locomotor activity) of anxiety-like behavior. Results: Intra-BLA administration of histamine (2.5 and 5μg/rat) decreased %OAT [P <0.001]. Histamine (5μg/rat) also reduced %OAE [P <0.05] but not locomotor activity. The results obtained may indicate an anxiolytic response for histamine. Furthermore, bilateral intra-BLA microinjections of different doses of l-arginine (l-arg), an NO precursor (0.5 and 1μg/rat) increased %OAT [P <0.01], %OAE [P <0.01] and locomotor activity [P <0.001] while NG-nitro-l-arg methylester (l-NAME), a potent inhibitor of NO-synthase (NOS; 0.025, 0.05 and 0.1μg/rat) decreased %OAT [P <0.05] and locomotor activity [P <0.001] but not %OAE. The combination of l-arg (0.5μg/rat) with histamine increased %OAE [P <0.001] but had no effect on %OAT and locomotor activity. Finally, the combination of l-NAME (0.025μg/rat) with histamine decreased %OAT [P <0.001] and locomotor activity [P <0.05] but increased %OAE. Conclusion: The results indicate a modulatory role for NO in BLA in the anxiogenic response of histamine in rats. [ABSTRACT FROM AUTHOR]

Abstract: Cyclosporine A (CyA) leads to liver injury, probably by causing the production of free radicals and resulting in nitric oxide (NO) deficiency. We evaluated CyA-mediated liver damage histopathologically to determine the possible beneficial effects of l-arginine (l-Arg). In this study, 7 groups of Sprague–Dawley rats; (1) Control group; (2) 0.9% NaCl group; (3) CyA group: 7.5mg/kg/day; (4) l-Arg group: 2g/lt/day; (5) l-NAME (N-nitro-l-arginine methyl ester) group: 5mg/100ml/day; (6) CyA+l-Arg group: l-Arg (2g/lt/day)+CyA (7.5mg/kg/day); and (7) CyA+l-NAME group: CyA (7.5mg/kg/day)+l-NAME (5mg/100ml/day) were included. At the end of the treatments, animals were killed and hepatic tissues were treated for morphological (hematoxylin and eosin) and biochemical (NO and malondialdehyde, MDA) analyses, and serum was processed for biochemical (alanine transaminase (ALT), aspartate transaminase (AST), bilirubin, alkaline phosphatase (ALP) and total protein) study. The results indicated that CyA-induced hepatotoxicity was characterized by sinusoidal dilatation, hepatocellular vacuolization, neutrophilic infiltration and hepatocellular necrosis. These findings were less pronounced in the CyA+l-Arg group than CyA alone group. l-NAME group showed moderate changes. The CyA+l-NAME (Group 7) had more severe changes. We found changes in tissue NO and MDA levels. We think that the tissue damage caused by CyA is mild and reversible at the period when biochemical parameters are just starting to become abnormal and that l-Arg may have a protective effect against CyA damage on liver. [Copyright &y& Elsevier]

Abstract: Arginine deiminase (ADI), currently in clinical trials, has various biological activities including anti-proliferation, anti-angiogenesis and inhibition of inducible nitric oxide synthase (iNOS). To recognize limitations and therapeutic applications, the mechanism of ADI modulation of arginine metabolic pathways was investigated. MCF-7 and A549 cells have notable different sensitivity to recombinant ADI (rADI) and express diverse argininosuccinate synthase (AS) activity, which regenerates arginine. Due to compartmentalization of arginine, utilization of arginine for protein synthesis occurs from either the intracellular arginine pool or the citrulline–arginine-regeneration pathway, whereas for polyamine synthesis, utilization is only from the intracellular arginine pool. Modulating AS activity or introducing rADI intracellularly to reduce intracellular arginine regeneration may expand therapeutic applications of rADI. [Copyright &y& Elsevier]

• Ordered structures of myosin were converted to disordered structures by L-Arg. • The effect was more obvious on rod-rod cross-linking than head-head aggregation. • Increasing pH induced by L-Arg increased the electrostatic repulsion of myosin. • The cationic L-Arg interacted with anionic groups on the myosin at neutral pH. • Heat-induced phase separation of myosin was ameliorated by L-Arg. This investigation aimed to study the potential mechanism of L-arginine (L-Arg) on the heat-induced phase separation phenomenon of myosin from the perspective of conformational changes of myosin. L-Arg ameliorated the phase separation of myosin after a two-step heating procedure via suppression of heat-induced aggregation of myosin. The effect of L-Arg on the heating of myosin at high temperatures (75–85 °C) was more pronounced than that in the setting stage (35–45 °C), suggesting that the ameliorative effects of L-Arg on the heat-induced phase separation of myosin are mainly attributed to the inhibition of rod-rod cross-linking between denatured myosin molecules. Additionally, L-Arg without pH modification exhibited an increased ability to suppress the gelation of myosin compared with pH modification, indicating that both pH effects and the particular structure of L-Arg play noticeable roles in the suppression of myosin gelation. Far-UV circular dichroism, intrinsic fluorescence spectroscopy and differential scanning calorimetry demonstrated that L-Arg induced the absence of ordered secondary structures of myosin molecules, especially β-sheets, and thus generated a looser protein structure, which may represent the dominant suppression mechanisms of L-Arg on the heat-induced aggregation of myosin. This work provided support for the use of L-Arg as a food additive, and the results of this study will be attractive to the meat and beverage products. [ABSTRACT FROM AUTHOR]

• We predicted the binding capacity of peptide aptamers by molecular docking. • We conducted ITC assay to identify peptide aptamers that bind to l -arginine. • A promising amino acid biosensor based on the identified peptide was obtained. As a primary building block for protein synthesis, l -arginine (l -Arg) is also a precursor for the synthesis of important metabolites, and is involved in various physiological and pathophysiological processes. l -Arg is a potential biomarker in clinical diagnosis and nutritional status assessment, making it valuable to quantify and monitor this biomolecule. In this study, peptide aptamers that specifically interact with l -Arg were identified by high-throughput molecular docking, and the binding capacities between the synthesized peptide aptamers and l -Arg were then measured by isothermal titration calorimetry. We hypothesized that the peptide aptamer with the greatest binding capacity could be used as the recognition element in a biosensor. A chemosynthetic peptide aptamer modified with mercaptan and spacer units (thioctic acid-GGGG-FGHIHEGY) was thus used to construct label-free electrochemical impedimetric biosensors for l -Arg based on gold electrodes. The optimum biosensor showed good sensitivity to l -Arg with a linear range of 0.1 pM–0.1 mM, and the calculated limit of detection (three times the signal-to-noise ratio) was 0.01 pM. Interference studies and assays of diluted serum samples were also carried out, and satisfactory results obtained. In conclusion, a potential method of peptide aptamer screening and biosensor fabrication for detecting small biological molecules was demonstrated. [ABSTRACT FROM AUTHOR]

L-arginine (L-Arg) depletion induced by randomly PEGylated arginine deiminase (ADI-PEG20) can treat arginosuccinate synthase (ASS)-negative cancers, and ADI-PEG20 is undergoing phase III clinical trials. Unfortunately, ASS-positive cancers are resistant to ADI-PEG20. Moreover, the yield of ADI production is low because of the formation of inclusion bodies. Here, we report a thermostable arginine-depleting enzyme, Bacillus caldovelox arginase mutant (BCA-M: Ser161->Cys161). An abundant amount of BCA-M was easily obtained via high cell-density fermentation and heat treatment purification. Subsequently, we prepared BCA-M-PEG20, by conjugating a single 20 kDa PEG monomer onto the Cys161 residue via thio-chemistry. Unlike ADI-PEG20, BCA-M-PEG20 significantly inhibited ASS-positive lung cancer cell growth. Pharmacodynamic studies showed that a single intraperitoneal injection (i.p). administration of 250 U/mouse of BCA-M-PEG20 induced low L-Arg level over 168 h. The mono-PEGylation of BCA-M prolonged its elimination half-life from 6.4 to 91.4 h (a 14-fold increase). In an A549 lung cancer xenograft model, a weekly administration of 250 U/mouse of BCA-M-PEG20 suppressed tumor growth significantly. We also observed that BCA-M-PEG20 did not cause any significant safety issue in mouse models. Overall, BCA-M-PEG20 showed excellent results in drug production, potency, and stability. Thereby, it has great potential to become a promising candidate for lung cancer therapy. [ABSTRACT FROM AUTHOR]

Neuronal nitric oxide synthase μ (nNOSμ) contains 34 additional residues in an autoregulatory element compared to nNOSα. Cytochrome c and flavin reductions in the absence of calmodulin (CaM) were faster in nNOSμ than nNOSα, while rates in the presence of CaM were smaller. The magnitude of stimulation by CaM is thus notably lower in nNOSμ. No difference in NO production was observed, while electron transfer between the FMN and heme moieties and formation of an inhibitory ferrous-nitrosyl complex were slower in nNOSμ. Thus, the insert affects electron transfer rates, modulation of electron flow by CaM, and heme-nitrosyl complex formation., (© 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Previous studies have shown that nitric oxide (NO) inhibits apoptosis of retinal neurons in culture through the canonical cyclic GMP/protein kinase G (PKG)-dependent pathway, but also involving multiple kinase pathways, such as phosphatidylinositol 3' kinase (PI3k) and AKT. NO and AKT exhibit survival-promoting properties and display important roles in both CNS development and plasticity. The purpose of this study was to evaluate the effects of exogenous NO, derived from the NO donor S-nitroso-N-acetylpenicillamin (SNAP), or endogenous NO, produced from l-arginine, on AKT phosphorylation in cultured chick retinal neurons. Our results demonstrate that SNAP or l-arginine enhances AKT phosphorylation on both serine-473 and threonine-308 residues in a concentration and time-dependent manner. This effect was mediated by the activation of soluble guanylyl cyclase and PKG, since it was blocked by the respective enzyme inhibitors ODQ or LY83583 and KT5823, as well as by transduction with shRNA lentiviruses coding PKGII shRNA, and mimicked by the respective enzyme activators YC-1 and 8-Bromo cyclic GMP, and also by the cyclic GMP phosphodiesterase inhibitor zaprinast. In addition, LY294002 or wortmannin suppressed the SNAP effect, indicating the involvement of phosphoinositide 3' kinase. Moreover, the mTOR inhibitor KU0063794 blocked SNAP-induced AKT phosphorylation at both residues, suggesting the participation of the mTORC2 complex in the process. Glutamate and NMDA also promoted AKT phosphorylation and a nitric oxide synthase inhibitor abrogated these effects, revealing a mechanism involving the activation of NMDA receptors and NO production. We have also found that SNAP and l-arginine induced AKT translocation into the nucleus of retinal neurons as well as other neuronal cell lines. SNAP also protects retinal cells from death induced by hydrogen peroxide and this effect was blocked by the phosphoinositide 3' kinase inhibitor LY294002. We therefore conclude that NO produced from endogenous or exogenous sources promotes AKT activation and its shuttling to the nucleus, probably participating in neuronal survival pathways important during CNS development., (© 2013.)

Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over-production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed., (© 2013.)