RESUMEN

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 µm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

Asunto(s)

Regeneración Ósea , Quitosano , Flavonoles , Hidrogeles , Sistema de Señalización de MAP Quinasas , Osteogénesis , Fosfatidilinositol 3-Quinasas , Polisacáridos , Proteínas Proto-Oncogénicas c-akt , Quitosano/química , Quitosano/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Flavonoles/farmacología , Flavonoles/química , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Arginina/química , Arginina/farmacología , Oxidación-Reducción/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Adhesivos/química , Adhesivos/farmacología

RESUMEN

The l -arginine ( l -Arg)/nitric oxide/cyclic GMP/potassium channel (K ATP ) pathway and opioid receptors are known to play critical roles in pain perception and the antinociceptive effects of various compounds. While there is evidence suggesting that the analgesic effects of rutin may involve nitric oxide modulation, the direct link between rutin and the l -Arg/nitric oxide/cyclic GMP/K ATP pathway in the context of pain modulation requires further investigation. The antinociceptive effect of rutin was studied in male NMRI mice using the formalin test. To investigate the role of the l -Arg/nitric oxide/cyclic GMP/K ATP pathway and opioid receptors, the mice were pretreated intraperitoneally with different substances. These substances included l -Arg (a precursor of nitric oxide), S-nitroso- N -acetylpenicillamine (SNAP, a nitric oxide donor), N(gamma)-nitro- l -arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), sildenafil (an inhibitor of phosphodiesterase enzyme), glibenclamide (a K ATP channel blocker), and naloxone (an opioid receptor antagonist). All pretreatments were administered 20 min before the administration of the most effective dose of rutin. Based on our investigation, it was found that rutin exhibited a dose-dependent antinociceptive effect. The administration of SNAP enhanced the analgesic effects of rutin during both the initial and secondary phases. Moreover, L-NAME, naloxone, and glibenclamide reduced the analgesic effects of rutin in both the primary and secondary phases. In conclusion, rutin holds significant value as a flavonoid with analgesic properties, and its analgesic effect is directly mediated through the nitric oxide/cyclic GMP/K ATP channel pathway.

Asunto(s)

Analgésicos , Arginina , GMP Cíclico , Canales KATP , NG-Nitroarginina Metil Éster , Óxido Nítrico , Receptores Opioides , Rutina , Transducción de Señal , Animales , Masculino , Ratones , Arginina/farmacología , Óxido Nítrico/metabolismo , Rutina/farmacología , Analgésicos/farmacología , Transducción de Señal/efectos de los fármacos , Receptores Opioides/metabolismo , Receptores Opioides/efectos de los fármacos , Canales KATP/metabolismo , GMP Cíclico/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Gliburida/farmacología , Citrato de Sildenafil/farmacología , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Naloxona/farmacología , Sulfonas/farmacología , Piperazinas/farmacología , Purinas/farmacología , S-Nitroso-N-Acetilpenicilamina/farmacología , Dolor/tratamiento farmacológico , Dolor/metabolismo , Antagonistas de Narcóticos/farmacología , Relación Dosis-Respuesta a Droga , Donantes de Óxido Nítrico/farmacología

RESUMEN

The aim of this study was to assess the effect of adding arginine at different concentrations to commercial and experimental orthodontic resins on shear bond strength (SBS), as well as on the antimicrobial activity of arginine against S. mutans. Metal brackets were bonded onto the surface of 120 bovine incisors using Transbond, OrthoCem, and an experimental resin (ER), adding 0, 2.5, 5, and 7 wt.% of arginine. The SBS test was performed in deionized water at 37 ºC for 24 h, at 0.5 mm/min. SBS test results were subjected to two-way ANOVA and Tukey's test (α = 0.05). CFU/mL data (antimicrobial assessment) were assessed by Kruskal-Wallis and Dunn's tests (α = 0.05). No statistical difference between the resins was observed in untreated groups (p > 0.05). The addition of arginine at 2.5% (27.7 MPa) and 5% (29.0 MPa) increased the SBS of Transbond when compared (p < 0.05) to OrthoCem (18.5 and 15.6 MPa, respectively) and ER (16.3 and 18.1 MPa, respectively). Arginine at 7% improved the SBS of Transbond (24.1 MPa) and ER (21.0 MPa), which was statistically higher (p < 0.05) than OrthoCem (12.6 MPa). OrthoCem did not show a statistically significant difference at the three concentrations of arginine (p > 0.05). The addition of arginine to resins reduced the count of S. mutans (p < 0.05). As for ER, all concentrations of arginine significantly decreased CFU/mL (p < 0.05). Among commercial resins, only 7% of arginine significantly reduced CFU/mL. The addition of arginine did not interfere with the bond strength and demonstrated antibacterial activity against S. mutans.

Asunto(s)

Arginina , Ensayo de Materiales , Soportes Ortodóncicos , Cementos de Resina , Resistencia al Corte , Streptococcus mutans , Arginina/química , Arginina/farmacología , Animales , Bovinos , Streptococcus mutans/efectos de los fármacos , Análisis de Varianza , Cementos de Resina/química , Factores de Tiempo , Reproducibilidad de los Resultados , Propiedades de Superficie/efectos de los fármacos , Estadísticas no Paramétricas , Valores de Referencia , Recubrimiento Dental Adhesivo/métodos , Bisfenol A Glicidil Metacrilato

RESUMEN

Agricultural yields are often limited by damage caused by pathogenic microorganisms, including plant-pathogenic bacteria. The chemical control options to cope with bacterial diseases in agriculture are limited, predominantly relying on copper-based products. These compounds, however, possess limited efficacy. Therefore, there is an urgent need to develop novel technologies to manage bacterial plant diseases and reduce food loss. In this study, a new antimicrobial agent was developed using a doping method that entraps small bioactive organic molecules inside copper as the metal matrix. The food preservative agent lauroyl arginate ethyl ester (ethyl lauroyl arginate; LAE) was chosen as the doped organic compound. The new composites were termed LAE@[Cu]. Bactericidal assays against Acidovorax citrulli, a severe plant pathogen, revealed that LAE and copper in the composites possess a synergistic interaction as compared with each component individually. LAE@[Cu] composites were further characterised in terms of chemical properties and in planta assays demonstrated their potential for further development as crop protection agents.

Asunto(s)

Cobre , Protección de Cultivos , Enfermedades de las Plantas , Cobre/química , Cobre/farmacología , Protección de Cultivos/métodos , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Comamonadaceae/efectos de los fármacos , Comamonadaceae/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Arginina/química , Arginina/farmacología , Arginina/análogos & derivados , Antibacterianos/farmacología , Antibacterianos/química , Viabilidad Microbiana/efectos de los fármacos

RESUMEN

Obesity and its associated disorders, such as hyperlipidemia, have become a global issue following the consumption of unhealthy, high-fat, and high- carbohydrate foods, which burdens the economies and the health systems of human societies worldwide. This study aimed to evaluate the effect of oral consumption of 6-gingerol and L-arginine supplements on obesity factors. Thirty rats in five groups were fed a diet specific to each group for 12 weeks and then treated with the oral administration of L-arginine (200 mg/day) and 6-gingerol (100 mg/day) for 12 weeks. The food and water intake and weight change, were then measured. In addition, plasma glucose, triglyceride, cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL) , low-density lipoprotein (LDL), and serum hormone levels, including corticosterone, testosterone, and insulin, were measured, and NPY, Y1, and Y5 receptor gene expression were recorded using real-time PCR. Administration of 6-gingerol and L-arginine decreased food intake, weight gain, glucose levels, insulin levels, and homeostasis model assessment-insulin resistance (HOMA-IR) index compared to the HCD control group. In addition, corticosterone and testosterone levels in the study groups showed a significant decrease (P<0.05) and increase (P<0.01) compared to the control groups, respectively. Triglyceride, total cholesterol, HDL, and VLDL levels in the groups treated with L-arginine and gingerol alone or combined significantly decreased compared to the control group (P<0.01). This study confirms that 6-gingerol and L-arginine supplements prevent HCD-induced hyperlipidemia by controlling hormones and neurotransmitters involved in the general metabolism. .

Asunto(s)

Arginina , Catecoles , Suplementos Dietéticos , Alcoholes Grasos , Obesidad , Animales , Alcoholes Grasos/farmacología , Alcoholes Grasos/administración & dosificación , Arginina/administración & dosificación , Arginina/farmacología , Masculino , Catecoles/farmacología , Catecoles/administración & dosificación , Obesidad/metabolismo , Ratas , Suplementos Dietéticos/análisis , Ratas Wistar , Regulación de la Expresión Génica/efectos de los fármacos

RESUMEN

A total of 480 newly weaned pigs (PIC 337 × 1050; Genus, Hendersonville, TN) with an initial body weight (BW) of 6.20 ±â€…0.61 kg were used in a dose-response study to investigate the impact of increasing standardized ileal digestible (SID) Arg:Lys on nursery pig growth performance. At weaning, pigs were placed into 48 pens with 5 barrows and 5 gilts per pen. Pens were randomly assigned to 1 of 6 dietary treatments. The experimental diets were formulated with increasing SID Arg:Lys, achieved by substituting corn starch, glycine, and l-alanine with l-arginine, resulting in SID Arg:Lys ranging from 45% to 145%. Diets were sublimiting in SID Lys and exceeded all other essential amino acid requirements. The experimental diets were fed across two feeding phases from days 0 to 10 and 10 to 27, with adjustments made to account for the Lys requirement of the pigs. All pens were placed on a common diet for the remaining 14 d of the study to evaluate carryover effects. Pigs and feeders were weighed at the start and end of each phase to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Data were analyzed according to a linear regression model, which included the linear and quadratic effects of SID Arg:Lys and initial BW. Pen was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.50 < P ≤ 0.10. From days 0 to 27, Arg:Lys tended to have a quadratic effect on ADFI (P = 0.058), where 97.00 ±â€…7.631% SID Arg:Lys maximized feed intake. Similarly, Arg:Lys had a quadratic impact on ADG (P = 0.046), where ADG was maximized at a SID Arg:Lys of 95.65 ±â€…7.165. Correspondingly, Arg:Lys had a quadratic effect on pig BW on day 27 (P = 0.014). These effects were carried through the end of the study, where Arg:Lys quadratically impacted days 0 to 41 ADFI (P = 0.006), ADG (P = 0.077), and day 41 BW (P = 0.028). There was no evidence of an effect of SID Arg:Lys on G:F throughout the study (P ≥ 0.315). In conclusion, SID Arg:Lys quadratically impacted ADFI and ADG in 6- to 13-kg nursery pigs, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]), and ADG was maximized at a SID Arg:Lys of 95.65% (95% CI [81.2%, 110.1%]). Together, these data suggest that the SID Arg:Lys requirement of nursery pigs is at least 81%, based on the lower bounds of the 95% CI for maximum ADG and ADFI, and excessive Arg supplementation may negatively affect growth performance.

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Arginine is considered a conditionally essential amino acid (EAA) in swine, meaning that under certain circumstances, the rate of Arg utilization is greater than endogenous synthesis, resulting in a dietary Arg requirement to meet the pig's needs for growth and other biological functions. Our group and others have shown benefits to feeding Arg levels above the NRC (2012) estimated requirement; however, there has been a lack of research to determine the SID Arg requirement relative to lysine in young pigs. Therefore, the objective of this study was to determine the optimal dietary SID Arg:Lys to maximize growth performance in 6- to 13-kg nursery pigs. In the current trial, average daily gain (ADG) and average daily feed intake (ADFI) responded quadratically to increasing SID Arg:Lys from 45% to 145%, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]) and ADG was maximized at 95.65% (95% CI [81.2%, 110.1%]). Together, the results of this study suggest the SID Arg:Lys requirement of 6- to 13-kg nursery pigs is at least 81%, based on the lower bounds of the 95% confidence intervals for maximum ADG and ADFI, but excess supplementation may reduce performance.

Asunto(s)

Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Arginina , Dieta , Lisina , Animales , Arginina/farmacología , Arginina/administración & dosificación , Dieta/veterinaria , Alimentación Animal/análisis , Lisina/administración & dosificación , Lisina/farmacología , Masculino , Femenino , Porcinos/crecimiento & desarrollo , Porcinos/fisiología , Íleon/fisiología , Íleon/efectos de los fármacos , Digestión/efectos de los fármacos , Distribución Aleatoria , Suplementos Dietéticos/análisis , Aumento de Peso/efectos de los fármacos

RESUMEN

Biotin and arginine play crucial roles in lipid metabolism and may offer promising interventions against obesity. This study examined the combined effect of magnesium biotinate (MgB) and inositol-stabilized arginine silicate complex (ASI) on obesity-related oxidative imbalance, inflammation, lipid metabolism and neuromodulation in rats on a high-fat diet (HFD). Forty rats were divided into five groups: (a) control: rats were fed a standard diet containing 12% of energy from fat; (b) HFD: rats were fed the HFD with 42% of energy from fat; (c) HFD + MgB: rats were fed the HFD and given 0.31 mg/kg body weight (BW) MgB, (d) HFD + ASI: rats were fed the HFD and were given 12.91 mg/kg BW ASI), and (e) HFD + MgB + ASI: rats were fed the HFD and given 0.31 mg/kg BW MgB and 12.91 mg/kg BW ASI). The combined administration of MgB and ASI reduced the levels of serum cholesterol, free fatty acid (FFA), and malondialdehyde (MDA), as well as liver inflammatory cytokines, sterol regulatory element-binding protein 1-c (SREBP-1c), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) proteins (P < 0.001) compared to HFD rats without supplementation. Moreover, this combination increased the activities of antioxidant enzymes (P < 0.05) and boosted the brain-derived neurotrophic factor (BDNF), serotonin, dopamine (P < 0.001), as well as liver insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < 0.001). These findings suggest that combining MgB and ASI could deter liver fat accumulation and enhance lipid metabolism in HFD-fed rats by modulating various metabolic pathways and neuromodulators related to energy metabolism. This combination demonstrates potential in addressing obesity and its related metabolic dysfunctions.

Asunto(s)

Antioxidantes , Arginina , Dieta Alta en Grasa , Animales , Dieta Alta en Grasa/efectos adversos , Ratas , Arginina/farmacología , Arginina/metabolismo , Masculino , Antioxidantes/farmacología , Antioxidantes/metabolismo , Silicatos/farmacología , Obesidad/metabolismo , Inflamación/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Neurotransmisores/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad

RESUMEN

OBJECTIVE: L-arginine is a semi-essential amino acid produced by the body which has an important role in the process of stem cell regeneration. However, under inflammatory conditions, denaturation of pulp amino acids and proteins occurr resulting in a decrease in the ability of stem cells to self-renew. Therefore, in this study, L-arginine was added in vitro to the culture media Dulbecco's Modified Eagle Medium - (DMEM) of human dental pulp stem cells (hDPSCs) to analyse the potential of L-arginine on migration and proliferation by comparing between 3 concentrations, namely 300, 400, 500 µmol/L and control group (DMEM), to obtain the most optimal concentration for proliferation and migration. METHODS: Serum-starved hDPSCs were divided into four groups: control: hDPSCs in DMEM; hDPSCs in 300 µmol/L of the L-Arginine based culture media group; hDPSCs in 400 µmol/L of the L-Arginine based culture media group; and hDPSCs in 500 µmol/L of the L-Arginine based culture media group, which were added in two separate 24-well-plates (5×104 cell/well) for proliferation and migration evaluation. The proliferation of all groups was measured by using a cell count test (haemacytometer and manual checker) after 24 h. The migratory speed rate of all groups was measured by using cell migration assay (scratch wound assay) after 24 h. Cell characteristics were evaluated under microscope that was then evaluated using image-J® interpretation. This image J represented the measurement of migratory speed rate (nm/h) data. Statistical analysis was conducted using one-way ANOVA and post hoc Bonferroni (p<0.05) for proliferation and post hoc LSD (p<0.05) for migration. RESULTS: There was a statistically significant difference in hDPSCs proliferation among various concentration groups of the L-Arginine based solution (300, 400 and 500 µmol/L) compared to the control group (p<0.05). There was a statistically significant difference in the migratory speed rate of hDPSCs at 500 µmol/L of the L-Arginine based solution group compared to lower concentrations and control group (p<0.05). CONCLUSION: All three concentrations of L-arginine can induce proliferation of hDPSCs. L-arginine at 500 µmol/L can induce higher hDPSCs proliferation and faster migration at 24 hours compared to lower concen-trations and control.

Asunto(s)

Arginina , Movimiento Celular , Proliferación Celular , Pulpa Dental , Células Madre , Pulpa Dental/citología , Humanos , Arginina/farmacología , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Madre/efectos de los fármacos , Células Cultivadas

RESUMEN

We previously reported that a linear cationic 12-amino acid cell-penetrating peptide (CPP) was bactericidal for Neisseria gonorrhoeae. In this study, our objectives were to determine the effect of cyclization of the linear CPP on its antibacterial activity for N. gonorrhoeae and cytotoxicity for human cells. We compared the bactericidal effect of 4-hour treatment with the linear CPP to that of CPPs cyclized by a thioether or a disulfide bond on human challenge and multi-drug resistant (MDR) strains of N. gonorrhoeae grown in cell culture media with 10% fetal bovine serum (FBS). The effect of lipooligosaccharide (LOS) sialylation on bactericidal activity was analyzed. We determined the ability of the CPPs to treat human cells infected in vitro with N. gonorrhoeae, to reduce the inflammatory response of human monocytic cells to gonococci, to kill strains of three commensal Neisseria species, and to inhibit gonococcal biofilms. The cyclized CPPs killed 100% of gonococci from all strains at 100 µM and >90% at 20 µM and were more potent than the linear form. The thioether-linked but not the disulfide-linked CPP was less cytotoxic for human cervical cells compared to the linear CPP. LOS sialylation had minimal effect on bactericidal activity. In treating infected human cells, the thioether-linked CPP at 20 µM killed >60% of extra- and intracellular bacteria and reduced TNF-α expression by THP-1 cells. The potency of the CPPs for the pathogenic and the commensal Neisseria was similar. The thioether-linked CPP partially eradicated gonococcal biofilms. Future studies will focus on determining efficacy in the female mouse model of gonorrhea.IMPORTANCENeisseria gonorrhoeae remains a major cause of sexually transmitted infections with 82 million cases worldwide in 2020, and 710,151 confirmed cases in the US in 2021, up 25% from 2017. N. gonorrhoeae can infect multiple tissues including the urethra, cervix, rectum, pharynx, and conjunctiva. The most serious sequelae are suffered by infected women as gonococci ascend to the upper reproductive tract and cause pelvic inflammatory disease, chronic pelvic pain, and infertility in 10%-20% of women. Control of gonococcal infection is widely recognized as increasingly challenging due to the lack of any vaccine. N. gonorrhoeae has quickly developed resistance to all but one class of antibiotics and the emergence of multidrug-resistant strains could result in untreatable infections. As such, gonorrhea is classified by the Center for Disease Control (CDC) as an urgent public health threat. The research presented herein on new therapeutics for gonorrhea has identified a cyclic cell-penetrating peptide (CPP) as a potent molecule targeting N. gonorrhoeae.

Asunto(s)

Antibacterianos , Péptidos de Penetración Celular , Gonorrea , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Humanos , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Péptidos de Penetración Celular/farmacología , Péptidos de Penetración Celular/química , Antibacterianos/farmacología , Antibacterianos/química , Animales , Ratones , Femenino , Biopelículas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ciclización , Lipopolisacáridos/metabolismo , Arginina/farmacología , Arginina/química

RESUMEN

RATIONALE: The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a key structure in panic. OBJECTIVES: To evaluate the role of nitric oxide (NO) in defensive behaviour and antinociception. METHODS: Either Nω-propyl-L-arginine (NPLA) or Carboxy-PTIO was microinjected in the PrL cortex, followed by hypothalamic treatment with bicuculline. The exploratory behaviours, defensive reactions and defensive antinociception were recorded. Encephalic c-Fos protein was immunolabelled after escape behaviour. RESULTS: NPLA (an inhibition of nNOs) decreased panic-like responses and innate fear-induced antinociception. The c-PTIO (a membrane-impermeable NO scavenger) decreased the escape behaviour. PrL cortex pre-treatment with c-PTIO at all doses decreased defensive antinociception. c-Fos protein was labelled in neocortical areas, limbic system, and mesencephalic structures. CONCLUSION: The NPLA and c-PTIO in the PrL/mPFC decreased the escape behaviour and defensive antinociception organised by medial hypothalamic nuclei. The oriented escape behaviour recruits neocortical areas, limbic system, and mesencephalic structures. These findings suggest that the organisation of defensive antinociception recruits NO-signalling mechanisms within the PrL cortex. Furthermore, the present findings also support the role of NO as a retrograde messenger in the PrL cortex during panic-like emotional reactions.

Asunto(s)

Óxido Nítrico , Pánico , Corteza Prefrontal , Proteínas Proto-Oncogénicas c-fos , Ratas Wistar , Animales , Masculino , Óxido Nítrico/metabolismo , Pánico/fisiología , Pánico/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de los fármacos , Arginina/farmacología , Arginina/análogos & derivados , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Reacción de Fuga/fisiología , Reacción de Fuga/efectos de los fármacos , Bicuculina/farmacología , Benzoatos , Imidazoles

RESUMEN

Impaired wound healing in diabetic wounds is common due to infection, inflammation, less collagen synthesis, and vascularization. Diabetic wound healing in patients is still a challenge and needs an ideal wound dressing to treat and manage diabetic wounds. Herein, an efficacious wound dressing biomaterial was fabricated by cross-linking oxidized isabgol (Oisab) and chitosan (Cs) via trisodium trimetaphosphate and Schiff base bonds. l-Arginine (l-Arg) was incorporated as a bioactive substance in the Oisab + Cs scaffold to promote cell adhesion, cell proliferation, collagen synthesis, and vascularization. The fabricated scaffolds showed microporous networks in the scanning electron microscopy analysis. The scaffold also possessed excellent hemocompatibility. In vitro studies using fibroblasts (L929 and human dermal fibroblast cells) confirmed the cytocompatibility of these scaffolds. The results of the in vivo chicken chorioallantoic membrane assay confirmed the proangiogenic activity of the Oisab + Cs + l-Arg scaffolds. The wound-healing potential of these scaffolds was studied in streptozotocin-induced diabetic rats. This in vivo study showed that the period of epithelialization in the Oisab + Cs + l-Arg scaffold-treated wounds was 21.67 ± 1.6 days, which was significantly faster than the control (30.33 ± 2.5 days). Histological and immunohistochemical studies showed that the Oisab + Cs + l-Arg scaffolds significantly accelerated the rate of wound contraction by reducing inflammation, improving collagen synthesis, and promoting neovascularization. These findings suggest that the Oisab + Cs + l-Arg scaffolds could be beneficial in treating diabetic wounds in clinical applications.

Asunto(s)

Arginina , Quitosano , Colágeno , Diabetes Mellitus Experimental , Ensayo de Materiales , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas , Colágeno/química , Arginina/química , Arginina/farmacología , Andamios del Tejido/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Humanos , Masculino , Tamaño de la Partícula , Neovascularización Fisiológica/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Ratones , Ratas Sprague-Dawley , Oxidación-Reducción

RESUMEN

Mucogingival surgery has been widely used in soft gingival tissue augmentation in which autografts are predominantly employed. However, the autografts face grand challenges, such as scarcity of palatal donor tissue and postoperative discomfort. Therefore, development of alternative soft tissue substitutes has been an imperative need. Here, we engineered an interconnected porous bovine serum albumin methacryloyl (BSAMA: B, as a drug carrier and antioxidant)/gelatin methacryloyl (GelMA: G, as a biocompatible collagen-like component)-based cryogel with L-Arginine (Arg) loaded as an angiogenic molecule, which could serve as a promising gingival tissue biohybrid scaffold. BG@Arg cryogels featured macroporous architecture, biodegradation, sponge-like properties, suturability, and sustained Arg release. Moreover, BG@Arg cryogels promoted vessel formation and collagen deposition which play an important role in tissue regeneration. Most interestingly, BG@Arg cryogels were found to enhance antioxidant effects. Finally, the therapeutic effect of BG@Arg on promoting tissue regeneration was confirmed in rat full-thickness skin and oral gingival defect models. In vivo results revealed that BG@Arg2 could promote better angiogenesis, more collagen production, and better modulation of inflammation, as compared to a commercial collagen membrane. These advantages might render BG@Arg cryogels a promising alternative to commercial collagen membrane products and possibly autografts for soft gingival tissue regeneration.

Asunto(s)

Arginina , Criogeles , Gelatina , Encía , Regeneración , Albúmina Sérica Bovina , Andamios del Tejido , Criogeles/química , Animales , Arginina/química , Arginina/farmacología , Ratas , Gelatina/química , Regeneración/efectos de los fármacos , Albúmina Sérica Bovina/química , Andamios del Tejido/química , Cicatrización de Heridas/efectos de los fármacos , Metacrilatos/química , Bovinos , Porosidad , Masculino , Antioxidantes/farmacología , Antioxidantes/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Ratas Sprague-Dawley

RESUMEN

Androgenic alopecia (AGA) typically manifests post-puberty, resulting in decreases in hair density, disruptions in the hair growth cycle, and alterations in hair follicle micro structure. Dihydrotestosterone (DHT) is a key hormone implicated in hair loss, especially on male. In this study, we found that each of arginine (Arg), arterial extract (AE) or biotin tripeptide-1 (BT-1), when combined with low level light therapy (LLLT, at 630 nm, 2 J/cm2), showed the efficacy in enhancing mitochondrial functions, cell proliferation and collagen synthesis in fibroblasts. Additionally, CARRIPOWER (the complexes of AE, BT-1, Arg, and Diaminopyrimidine derivatives), in conjunction with LLLT (630 nm, 2 J/cm2), showed promising results in dermal papilla cells (DPCs). The promising results contained not also inflammatory cytokines (IL-1ß and IL-6) and cell pro apoptotic factor (TGF-ß2) reduction, but also Wnt pathway inhibition by decreasing DKK1 level, and pro-hair growth factors (vascular endothelial growth factor (VEGF) and ß-catenin) increase. This innovative combination therapy offers a potential solution for the treatment of AGA, addressing both hormonal and cellular factors involved in hair loss.

Asunto(s)

Proliferación Celular , Fibroblastos , Cabello , beta Catenina , Humanos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Fibroblastos/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de la radiación , Fibroblastos/efectos de los fármacos , beta Catenina/metabolismo , Cabello/efectos de la radiación , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Arginina/química , Arginina/farmacología , Alopecia/terapia , Folículo Piloso/efectos de la radiación , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Terapia por Luz de Baja Intensidad , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Oligopéptidos/química , Oligopéptidos/farmacología , Masculino , Colágeno/metabolismo , Colágeno/química , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/efectos de la radiación , Línea Celular , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/efectos de la radiación

RESUMEN

OBJECTIVES: The aim of this study was to quantitatively and comprehensively investigate the combined effects of arginine and fluoride on the suppression of pathogenicity using an in situ biofilm model and next-generation sequencing (NGS). METHODS: Using the in situ model, dental biofilms were formed and the viable bacterial counts and arginine activity in the arginine- and fluoride-containing dentifrice and control groups were measured. We also compared their effects on the bacterial microbiota and predictive functional factors in the control, arginine (arg), and arginine + fluoride (argF) groups using NGS analysis. RESULTS: Compared to the control treatment, the use of 8 % arginine and 1450 ppm fluoride toothpaste resulted in significantly high oral NH4+ concentrations without affecting the number of viable bacteria (P < 0.05). NGS analysis revealed that the oral microbiota of the control, arg, and argF groups were significantly different. Heat map analysis of the predicted functional factors revealed that the arg group had different properties from the other groups and activated specific substrate metabolic pathways; contrastingly, argF treatment inhibited the activity of these pathways and prevented an increase in the abundance of bacterial genera that utilize substrates such as sucrose, suggesting the synergistic effect of arginine and fluoride. CONCLUSIONS: This study indicates that the combination of arginine and fluoride has a synergistic effect on the bacterial microbiota and pathogenicity of dental biofilms compared with arginine alone. CLINICAL SIGNIFICANCE: Our findings suggest that the combination of arginine and fluoride could be used as an effective prebiotic and may inhibit the growth of bacteria associated with dental diseases.

Asunto(s)

Arginina , Biopelículas , Cariostáticos , Fluoruros , Pastas de Dientes , Arginina/farmacología , Biopelículas/efectos de los fármacos , Humanos , Fluoruros/farmacología , Pastas de Dientes/farmacología , Cariostáticos/farmacología , Sinergismo Farmacológico , Dentífricos/farmacología , Carga Bacteriana/efectos de los fármacos , Bacterias/efectos de los fármacos , Bacterias/clasificación , Microbiota/efectos de los fármacos , Placa Dental/microbiología , Adulto , Masculino , Adulto Joven , Secuenciación de Nucleótidos de Alto Rendimiento , Saliva/microbiología

RESUMEN

The avascular nature of cartilage tissue limits inherent regenerative capacity to counter any damage and this has become a substantial burden to the health of individuals. As a result, there is a high demand to repair and regenerate cartilage. Existing tissue engineering approaches for cartilage regeneration typically produce either microporous or nano-fibrous scaffolds lacking the desired biological outcome due to lack of biomimetic dual architecture of microporous construct with nano-fibrous interconnected structures like the native cartilage. Most of these scaffolds also fail to suppress ROS generation and provide sustained bioenergetics to cells, resulting in the loss of metabolic activity under avascular microenvironment of cartilage. A dual architecture microporous construct with nano-fibrous interconnected network of cellulose aerogel reinforced with arginine-coated graphene oxide (CNF-GO-Arg aerogel) was developed for cartilage regeneration. The designed dual-architectured CNF-GO-Arg aerogel using dual ice templating assembly demonstrates 80 % strain recovery ability under compression. The release of Arginine from CNF-GO-Arg aerogel supported 41 % reduction in intracellular ROS activity and promoted chondrogenic differentiation of hMSCs by shifting mitochondrial bioenergetics towards oxidative phosphorylation indicated by JC-1 dye staining. Overall developed CNF-GO-Arg aerogel provided multifunctionality via biomimetic morphology, cellular bioenergetics, and suppressed ROS generation to address the need for regeneration of cartilage.

Asunto(s)

Arginina , Cartílago , Celulosa , Grafito , Andamios del Tejido , Celulosa/química , Celulosa/farmacología , Grafito/química , Grafito/farmacología , Humanos , Andamios del Tejido/química , Arginina/química , Arginina/farmacología , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Ingeniería de Tejidos/métodos , Metabolismo Energético/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Especies Reactivas de Oxígeno/metabolismo , Condrogénesis/efectos de los fármacos , Geles/química , Regeneración/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología

RESUMEN

The mechanism connecting gut microbiota to appetite regulation is not yet fully understood. This study identifies specific microbial community and metabolites that may influence appetite regulation. In the initial phase of the study, mice were administered a broad-spectrum antibiotic cocktail (ABX) for 10 days. The treatment significantly reduced gut microbes and disrupted the metabolism of arginine and tryptophan. Consequently, ABX-treated mice demonstrated a notable reduction in feed consumption. The hypothalamic expression levels of CART and POMC, two key anorexigenic factors, were significantly increased, while orexigenic factors, such as NPY and AGRP, were decreased. Notably, the levels of appetite-suppressing hormone cholecystokinin in the blood were significantly elevated. In the second phase, control mice were maintained, while the ABX-treated mice received saline, probiotics, and short-chain fatty acids (SCFAs) for an additional 10 days to restore their gut microbiota. The microbiota reconstructed by probiotic and SCFA treatments were quite similar, while microbiota of the naturally recovering mice demonstrated greater resemblance to that of the control mice. Notably, the abundance of Akkermansia and Bacteroides genera significantly increased in the reconstructed microbiota. Moreover, microbiota reconstruction corrected the disrupted arginine and tryptophan metabolism and the abnormal peripheral hormone levels caused by ABX treatment. Among the groups, SCFA-treated mice had the highest feed intake and NPY expression. Our findings indicate that gut microbes, especially Akkermansia, regulate arginine and tryptophan metabolism, thereby influencing appetite through the microbe-gut-brain axis.

Asunto(s)

Microbioma Gastrointestinal , Metaboloma , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Ratones Endogámicos C57BL , Antibacterianos/farmacología , Triptófano/metabolismo , Apetito/efectos de los fármacos , Probióticos/farmacología , Arginina/farmacología , Arginina/metabolismo , Hipotálamo/metabolismo , Regulación del Apetito/fisiología , Ácidos Grasos Volátiles/metabolismo

RESUMEN

BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. METHODS: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate. RESULTS: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during per os lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats. CONCLUSION: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.

Asunto(s)

Arginina , Hipoxia , Plomo , Nitratos , Nitroarginina , Ratas Wistar , Animales , Arginina/metabolismo , Arginina/farmacología , Nitratos/metabolismo , Masculino , Ratas , Nitroarginina/farmacología , Hipoxia/metabolismo , Plomo/toxicidad , Hígado/metabolismo , Hígado/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Catalasa/metabolismo

RESUMEN

BACKGROUND: The continuous use of pesticides, such as dichlorvos, is a common agricultural and domestic practice. However, it is associated with shortfalls like testicular toxicity through the induction of oxidative stress-mediated signaling. On the other hand, L-arginine, a precursor of nitric oxide, has been reported to exert antioxidant activities and thus may attenuate dichlorvos-induced testicular toxicity. AIM: Hence, this study was designed to evaluate the effect of L-arginine treatment on dichlorvos-induced testicular toxicity. MATERIALS AND METHODS: Forty male Wistar rats were randomly assigned into four equal groups. The control rats were administered 0.5 mL of distilled water, dichlorvos- (DDVP-) treated rats were exposed to DDVP via inhalation for 15 min, DDVP + L-arginine-treated rats were exposed to DDVP and also received 100 mg/kg b.w/day, while L-arginine-treated rats received 100 mg/kg b.w/day. RESULTS: DDVP exposure significantly reduced testicular nitric oxide, relative testicular weight, lowered sperm count, viability, and motility, and suppressed serum FSH, LH, and testosterone levels. These findings were associated with a rise in testicular malondialdehyde, TNF-α, IL-6, and 8OHdG levels and caspase 3 activities, and a reduction in GSH and superoxide dismutase. Additionally, on histopathological examination, DDVP was observed to reduce mature sperm cells in the seminiferous tubular lumen and induce focal vascular congestion in the interstitial space. Nonetheless, L-arginine treatment significantly attenuated DDVP-induced biochemical and histological alterations. CONCLUSION: This study showed that L-arginine attenuated testicular toxicity by improving epididymal sperm variables and male sex hormones by suppressing oxidative stress, inflammation, and apoptosis in DDVP-exposed rats.

Asunto(s)

Apoptosis , Arginina , Caspasa 3 , Diclorvos , Estrés Oxidativo , Testículo , Animales , Masculino , Ratas , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Arginina/farmacología , Caspasa 3/metabolismo , Diclorvos/toxicidad , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Recuento de Espermatozoides , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Testosterona/sangre

RESUMEN

OBJECTIVES: To evaluate the in-vitro efficacy of inhibiting enamel demineralization using arginine in combination with fluoride-containing bioactive glass (FBG). METHODS: In this study, the healthy enamel blocks were first demineralized in acetic acid for 24 h, then soaked in anti-demineralization treatment solutions containing either arginine or FBG or both for 96 h.The specimens treated in acetic acid were applied as the control group. The pH, calcium and phosphorus ion concentrations of the solutions were measured before and after treatment. Changes in enamel mineral weight, microhardness, and composition were also analyzed. RESULTS: The present of arginine facilitated fluorine release from treatment solutions with the presence of FBG. Both arginine and FBG significantly increased the pH of treatment solutions and prevented the further mineral weight loss compared to the control group. All anti-demineralization treatment groups showed significant increases in microhardness, but there was no statistical difference among the treatment groups. The SEM analysis showed enamel restoration in the arginine and FBG groups upon treatment, while the combined groups showing a superior anti-demineralization efficacy. 19F NMR showed the formation of fluorapatite in samples treated with solutions containing FBG. CONCLUSIONS: Both arginine and FBG could inhibit enamel demineralization to some extent, and their combination demonstrated an enhanced anti-demineralization efficacy. The low-concentration combination group exhibited anti-demineralization effects comparable to those of high-concentration ones. CLINICAL SIGNIFICANCE: This study introduces a new approach for caries prevention by combining the application of arginine and FBG. The release of fluorine promoted by the presented arginine along with calcium and phosphorus ions from FBG facilitated FAP formation. Additionally, the increment of pH resulting from arginine and FBG degradation further prevents enamel demineralization.

Asunto(s)

Apatitas , Arginina , Calcio , Cariostáticos , Esmalte Dental , Fluoruros , Vidrio , Dureza , Fósforo , Desmineralización Dental , Arginina/uso terapéutico , Arginina/farmacología , Desmineralización Dental/prevención & control , Esmalte Dental/efectos de los fármacos , Concentración de Iones de Hidrógeno , Fluoruros/uso terapéutico , Vidrio/química , Calcio/análisis , Cariostáticos/farmacología , Cariostáticos/uso terapéutico , Fósforo/análisis , Humanos , Ensayo de Materiales , Flúor , Ácido Acético , Microscopía Electrónica de Rastreo , Cerámica , Animales

RESUMEN

OBJECTIVE(S): The study objective was to examine the effect of arginine (Arg) supplementation on the growth of probiotics. METHODS: Lacticaseibacillus rhamnosus GG, Lactiplantibacillus plantarum, and Lactobacillus acidophilus were identified as potential probiotics. L. rhamnosus GG and L. plantarum were selected for further experimentation. The probiotics were co-treated with 0.9 % NaCl (negative control), 0.5 % Arg, and 1.0 % Arg in a 1:1 ratio for 24 h at 5 % CO2, 37 °C. The probiotics were tested for growth profiles, spectroscopic turbidity assay, metabolic assays (XTT and WST-8), live/dead cell assessment using confocal laser scanning microscopy (CLSM), and colony forming units (CFU). RESULTS: The growth profiles of L. rhamnosus GG and L. plantarum were found to be similar, whereas L. acidophilus showed minimal or no transition from the initial lag phase. In the turbidity assay, the end-point absorbance for L. rhamnosus GG with 1.0 % Arg was significantly lower than 0.9 % NaCl and 0.5 % Arg (p < 0.05). For metabolic assays and CFU, increasing concentrations of Arg increased the viable cells for L. rhamnosus GG (p < 0.05), but decreased viability for L. plantarum (p < 0.05). Metabolic assays with dual-species bacterial suspensions indicated that Arg co-treatment inhibited viable proportions compared to control (p < 0.05). The dead cell proportion was significantly lower than live cell proportion for all tested interventions and probiotics (p < 0.05). CONCLUSION: Increasing concentrations of Arg promote the growth of L. rhamnosus GG, while conversely inhibiting the growth of L. plantarum. Therefore, the effect of prebiotic Arg on probiotics is concentration-dependent, leading to a selective promotion or inhibition of growth. CLINICAL SIGNIFICANCE: The present study results show that Arg supplementation can selectively enhance the growth of L. rhamnosus GG while inhibit the growth of L. plantarum. This underscores the need to consider strain-specific responses in probiotic formulations when developing Arg-based synbiotics for modulating biofilms and creating ecologically homeostatic biofilm microenvironments.

Asunto(s)

Arginina , Lacticaseibacillus rhamnosus , Lactobacillus acidophilus , Lactobacillus plantarum , Probióticos , Arginina/farmacología , Probióticos/farmacología , Lactobacillus acidophilus/efectos de los fármacos , Lactobacillus acidophilus/crecimiento & desarrollo , Lacticaseibacillus rhamnosus/efectos de los fármacos , Lactobacillus plantarum/crecimiento & desarrollo , Lactobacillus plantarum/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Recuento de Colonia Microbiana , Microscopía Confocal , Humanos