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Frontiers in Endocrinology 2024Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a...
Levels of asymmetric dimethylarginine in plasma and aqueous humor: a key risk factor for the severity of fibrovascular proliferation in proliferative diabetic retinopathy.
INTRODUCTION
Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a potential link between arginine pathway metabolites and diabetic retinopathy (DR). Connective tissue growth factor (CTGF) plays a role in the occurrence and development of fibrovascular proliferation (FVP) in PDR patients. However, the relationship between arginine pathway metabolites and FVP in PDR remains undefined. This study aimed to explore the correlation between four arginine pathway metabolites (arginine, asymmetric dimethylarginine[ADMA], ornithine, and citrulline) and the severity of FVP in PDR patients.
METHODS
In this study, plasma and aqueous humor samples were respectively collected from 30 patients with age-related cataracts without diabetes mellitus (DM) and from 85 PDR patients. The PDR patients were categorized as mild-to-moderate or severe based on the severity of fundal FVP. The study used Kruskal-Wallis test to compare arginine, ADMA, ornithine, and citrulline levels across three groups. Binary logistic regression identified risk factors for severe PDR. Spearman correlation analysis assessed associations between plasma and aqueous humor metabolite levels, and between ADMA and CTGF levels in aqueous humor among PDR patients.
RESULTS
ADMA levels in the aqueous humor were significantly greater in patients with severe PDR than in those with mild-to-moderate PDR(0.0004). However, the plasma and aqueous humor levels of arginine, ornithine, and citrulline did not significantly differ between mild-to-moderate PDR patients and severe PDR patients (0.05). Binary logistic regression analysis indicated that the plasma (0.01) and aqueous humor (0.006) ADMA levels in PDR patients were risk factors for severe PDR. Furthermore, significant correlations were found between plasma and aqueous humor ADMA levels (0.263, =0.015) and between aqueous humor ADMA and CTGF levels (0.837, <0.001).
CONCLUSION
Elevated ADMA levels in plasma and aqueous humor positively correlate with the severity of FVP in PDR, indicating ADMA as a risk factor for severe PDR.
Topics: Humans; Arginine; Male; Female; Diabetic Retinopathy; Middle Aged; Aqueous Humor; Risk Factors; Aged; Severity of Illness Index; Ornithine; Citrulline; Biomarkers; Connective Tissue Growth Factor
PubMed: 38933824
DOI: 10.3389/fendo.2024.1364609 -
International Journal of Nanomedicine 2024[This retracts the article DOI: 10.2147/IJN.S160848.].
Endogenous Ornithine Decarboxylase/Polyamine System Mediated the Antagonist Role of Insulin/PEG-CMCS Preconditioning against Heart Ischemia/Reperfusion Injury in Diabetes Mellitus [Retraction].
[This retracts the article DOI: 10.2147/IJN.S160848.].
PubMed: 38933417
DOI: 10.2147/IJN.S483384 -
Plants (Basel, Switzerland) Jun 2024In this study, processing tomato ( L.) 'Ligeer 87-5' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion...
In this study, processing tomato ( L.) 'Ligeer 87-5' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K, Ca, and Mg in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.
PubMed: 38931104
DOI: 10.3390/plants13121672 -
Plants (Basel, Switzerland) Jun 2024Salinity stress poses a significant threat to crop productivity worldwide, necessitating effective mitigation strategies. This study investigated the phytochemical...
Salinity stress poses a significant threat to crop productivity worldwide, necessitating effective mitigation strategies. This study investigated the phytochemical composition and potential of grape seed extract (GSE) to mitigate salinity stress effects on faba bean plants. GC-MS analysis revealed several bioactive components in GSE, predominantly fatty acids. GSE was rich in essential nutrients and possessed a high antioxidant capacity. After 14 days of germination, GSE was applied as a foliar spray at different concentrations (0, 2, 4, 6, and 8 g/L) to mitigate the negative effects of salt stress (150 mM NaCl) on faba bean plants. Foliar application of 2-8 g/L GSE significantly enhanced growth parameters such as shoot length, root length, fresh weight, and dry weight of salt-stressed bean plants compared to the control. The Fv/Fm ratio, indicating photosynthetic activity, also improved with GSE treatment under salinity stress compared to the control. GSE effectively alleviated the oxidative stress induced by salinity, reducing malondialdehyde, hydrogen peroxide, praline, and glycine betaine levels. Total soluble proteins, amino acids, and sugars were enhanced in GSE-treated, salt-stressed plants. GSE treatment under salinity stress modulated the total antioxidant capacity, antioxidant responses, and enzyme activities such as peroxidase, ascorbate peroxidase, and polyphenol oxidase compared to salt-stressed plants. Gene expression analysis revealed GSE (6 g/L) upregulated photosynthesis (chlorophyll a/b-binding protein of LHCII type 1-like () and ribulose bisphosphate carboxylase large chain-like ()) and carbohydrate metabolism (cell wall invertase I () genes) while downregulating stress response genes (ornithine aminotransferase () and ethylene-responsive transcription factor 1 ()) in salt-stressed bean plants. The study demonstrates GSE's usefulness in mitigating salinity stress effects on bean plants by modulating growth, physiology, and gene expression patterns, highlighting its potential as a natural approach to enhance salt tolerance.
PubMed: 38931028
DOI: 10.3390/plants13121596 -
Animals : An Open Access Journal From... Jun 2024Although both L-glutamate (Glu) and L-glutamine (Gln) have long been considered nutritionally nonessential in ruminants, these two amino acids have enormous nutritional... (Review)
Review
Although both L-glutamate (Glu) and L-glutamine (Gln) have long been considered nutritionally nonessential in ruminants, these two amino acids have enormous nutritional and physiological importance. Results of recent studies revealed that extracellular Gln is extensively degraded by ruminal microbes, but extracellular Glu undergoes little catabolism by these cells due to the near absence of its uptake. Ruminal bacteria hydrolyze Gln to Glu plus ammonia and, intracellularly, use both amino acids for protein synthesis. Microbial proteins and dietary Glu enter the small intestine in ruminants. Both Glu and Gln are the major metabolic fuels and building blocks of proteins, as well as substrates for the syntheses of glutathione and amino acids (alanine, ornithine, citrulline, arginine, proline, and aspartate) in the intestinal mucosa. In addition, Gln and aspartate are essential for purine and pyrimidine syntheses, whereas arginine and proline are necessary for the production of nitric oxide (a major vasodilator) and collagen (the most abundant protein in the body), respectively. Under normal feeding conditions, all diet- and rumen-derived Glu and Gln are extensively utilized by the small intestine and do not enter the portal circulation. Thus, de novo synthesis (e.g., from branched-chain amino acids and α-ketoglutarate) plays a crucial role in the homeostasis of Glu and Gln in the whole body but may be insufficient for maximal growth performance, production (e.g., lactation and pregnancy), and optimal health (particularly intestinal health) in ruminants. This applies to all types of feeding systems used around the world (e.g., rearing on a milk replacer before weaning, pasture-based production, and total mixed rations). Dietary supplementation with the appropriate doses of Glu or Gln [e.g., 0.5 or 1 g/kg body weight (BW)/day, respectively] can safely improve the digestive, endocrine, and reproduction functions of ruminants to enhance their productivity. Both Glu and Gln are truly functional amino acids in the nutrition of ruminants and hold great promise for improving their health and productivity.
PubMed: 38929408
DOI: 10.3390/ani14121788 -
BMC Plant Biology Jun 2024Salinity is a major abiotic stress, and the use of saline water in the agricultural sector will incur greater demand under the current and future climate changing...
BACKGROUND
Salinity is a major abiotic stress, and the use of saline water in the agricultural sector will incur greater demand under the current and future climate changing scenarios. The objective of this study was to develop a dual-functional nanofertilizer capable of releasing a micronutrient that nourishes plant growth while enhancing salt stress resilience in faba bean (Vicia faba L.).
RESULTS
Moringa oleifera leaf extract was used to synthesize sulfur nanoparticles (SNPs), which were applied as a foliar spray at different concentrations (0, 25, 50, and 100 mg/l) to mitigate the negative effects of salt stress (150 mM NaCl) on faba bean plants. The SNPs were characterized and found to be spherical in shape with an average size of 10.98 ± 2.91 nm. The results showed that salt stress had detrimental effects on the growth and photosynthetic performance (Fv/Fm) of faba bean compared with control, while foliar spraying with SNPs improved these parameters under salinity stress. SNPs application also increased the levels of osmolytes (soluble sugars, amino acids, proline, and glycine betaine) and nonenzymatic antioxidants, while reducing the levels of oxidative stress biomarkers (MDA and HO). Moreover, SNPs treatment under salinity stress stimulated the activity of antioxidant enzymes (ascorbate peroxidase (APX), and peroxidase (POD), polyphenol oxidase (PPO)) and upregulated the expression of stress-responsive genes: chlorophyll a-b binding protein of LHCII type 1-like (Lhcb1), ribulose bisphosphate carboxylase large chain-like (RbcL), cell wall invertase I (CWINV1), ornithine aminotransferase (OAT), and ethylene-responsive transcription factor 1 (ERF1), with the greatest upregulation observed at 50 mg/l SNPs.
CONCLUSION
Overall, foliar application of sulfur nanofertilizers in agriculture could improve productivity while minimizing the deleterious effects of salt stress on plants. Therefore, this study provides a strong foundation for future research focused on evaluating the replacement of conventional sulfur-containing fertilizers with their nanoforms to reduce the harmful effects of salinity stress and enhance the productivity of faba beans.
Topics: Vicia faba; Salt Stress; Sulfur; Nanoparticles; Fertilizers; Antioxidants; Plant Leaves; Photosynthesis
PubMed: 38926889
DOI: 10.1186/s12870-024-05270-7 -
Medicine Jun 2024Fahr syndrome is a rare, degenerative neurological condition characterized by bilateral idiopathic calcification of the periventricular region, especially the basal...
RATIONALE
Fahr syndrome is a rare, degenerative neurological condition characterized by bilateral idiopathic calcification of the periventricular region, especially the basal ganglia. This condition is often misdiagnosed as other neurological or psychiatric disorders due to its rarity and overlapping symptoms.
PATIENT CONCERNS
A 34-year-old man had been experiencing seizures and cognitive dysfunction for few years, which were further compounded by slurred speech and motor difficulties as acute conditions.
DIAGNOSIS
After investigations, severe hypocalcemia, and hypoparathyroidism were detected and his brain computed tomography showed extensive bilateral calcifications in basal ganglia, thalamus, dentate nuclei, and some parts of subcortical white matter, suggestive of Fahr syndrome. Although, the patient was initially misdiagnosed due to a lack of information and the rarity of this disease.
INTERVENTION
The patient was treated with intravenous calcium gluconate, vitamin D3, l-ornithine l-aspartate syrup, and levetiracetam, replacing carbamazepine.
OUTCOME
His symptoms, including slurred speech, muscle pain, and stiffness improved, serum calcium normalized, and he was discharged with medications for memory deficit and depression.
LESSONS
This case underscores the importance of raising awareness among physicians, especially in areas with limited medical resources, about the significance of prompt diagnosis and appropriate symptomatic treatment in enhancing patient prognosis and quality of life.
Topics: Humans; Male; Adult; Seizures; Cognitive Dysfunction; Calcinosis; Afghanistan; Basal Ganglia Diseases; Hypoparathyroidism; Hypocalcemia; Tomography, X-Ray Computed; Neurodegenerative Diseases
PubMed: 38905413
DOI: 10.1097/MD.0000000000038542 -
Applied and Environmental Microbiology Jun 2024uses allantoin as the sole nitrogen source during anaerobic growth. In the final step of allantoin degradation, oxamic transcarbamylase (OXTCase) converts oxalurate to...
uses allantoin as the sole nitrogen source during anaerobic growth. In the final step of allantoin degradation, oxamic transcarbamylase (OXTCase) converts oxalurate to carbamoyl phosphate (CP) and oxamate. The activity of this enzyme was first measured in in the 1960s, but no OXTCase enzyme or the encoding gene(s) have been found in any strain. This study discovered that (, , and ) are the genes that encode the global orphan enzyme OXTCase. The three genes form an operon together with (), encoding catabolic carbamate kinase. The operon is located directly downstream of the operon that encodes enzymes for the preceding steps of OXTCase. The OXTCase kinetic parameters were analyzed using the purified protein composed of AllF-AllG-AllH (FdrA-YlbE-YlbF); for the substrate CP, and were 1.3 mM and 15.4 U/mg OXTCase, respectively, and for the substrate oxamate, they were 36.9 mM and 27.0 U/mg OXTCase. In addition, the OXTCase encoded by the three genes is a novel transcarbamylase that shows no similarity with known enzymes of the transcarbamylase family such as aspartate transcarbamylase, ornithine transcarbamylase, and YgeW transcarbamylase. The present study elucidated the anaerobic allantoin degradation pathway of . Therefore, we suggest that the genes , , and are renamed , , and , respectively.IMPORTANCEThe anaerobic allantoin degradation pathway of includes a global orphan enzyme, oxamic transcarbamylase (OXTCase), which converts oxalurate to carbamoyl phosphate and oxamate. This study found that the (, , and ) genes encode OXTCase. The OXTCase activity and kinetics were successfully determined with purified recombinant AllF-AllG-AllH (FdrA-YlbE-YlbF). This OXTCase is a novel transcarbamylase that shows no similarity with known enzymes of the transcarbamylase family such as aspartate transcarbamylase (ATCase), ornithine transcarbamylase (OTCase), and YgeW transcarbamylase (YTCase). In addition, OXTCase activity requires three genes, whereas ATCase is encoded by two genes, and OTCase and YTCase are encoded by a single gene. The current study discovered OXTCase, the last unknown step in allantoin degradation, and this enzyme is a new member of the transcarbamylase group that was previously unknown.
PubMed: 38888336
DOI: 10.1128/aem.00957-24 -
L-arginine loading porous PEEK promotes percutaneous tissue repair through macrophage orchestration.Bioactive Materials Oct 2024Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high...
Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.
PubMed: 38882001
DOI: 10.1016/j.bioactmat.2024.05.025 -
The Journal of Biological Chemistry Jun 2024Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its...
Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its activity leads to diabetic complications. Here, we aimed to demonstrate that GL can serve as an indicator of the polyol pathway activity. Additionally, we propose a novel approach for detecting GL in peripheral blood samples using LC-MS/MS and evaluate its clinical usefulness. We successfully circumvent interference from fructoselysine, which shares the same molecular weight as GL, by performing ultrafiltration and hydrolysis without reduction, successfully generating adequate peaks for quantification in serum. Furthermore, using immortalized aldose reductase knockout mouse Schwann cells, we demonstrate that GL reflects the downstream activity of the polyol pathway and that GL produced intracellularly is released into the extracellular space. Clinical studies reveal that GL levels in patients with type 2 diabetes are significantly higher than those in healthy participants, while N-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1) levels are significantly lower. Both GL and MG-H1 show higher values among patients with vascular complications; however, GL varies more markedly than MG-H1 as well as hemoglobin A1c, fasting plasma glucose, and estimated glomerular filtration rate. Furthermore, GL remains consistently stable under various existing drug treatments for type 2 diabetes, whereas MG-H1 is impacted. To the best of our knowledge, we provide important insights in predicting diabetic complications caused by enhanced polyol pathway activity via assessment of GL levels in peripheral blood samples from patients.
PubMed: 38879006
DOI: 10.1016/j.jbc.2024.107479