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1.
Sci Rep ; 12(1): 7449, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523992

RESUMO

Adult wasps primary food resource is larval saliva. This liquid secretion consists mainly of amino acids and carbohydrates processed from the prey brought to the colony by the foragers. However, adults also regularly consume floral nectar. The nectar's most abundant proteinogenic amino acid is proline, and the two most abundant non-proteinogenic amino acids are ß-alanine and GABA. These three amino acids are also common in larval saliva. Here, we study the effect of these dietary amino acids on the physiology and nest construction behavior of the Oriental hornet. Our results reveal their deleterious effects, especially at high concentrations: ß-alanine and GABA consumption reduced the hornets' lifespan and completely inhibited their construction behavior; while proline induced a similar but more moderate effect. At low concentrations, these amino acids had no effect on hornet survival but did slow down the nest construction process. Using carbon isotopically labeled amino acids, we show that, unlike proline, ß-alanine is stored in most body tissues (brain, muscles, and fat body), suggesting that it is rapidly metabolized after consumption. Our findings demonstrate how a single amino acid can impact the fitness of a nectarivore insect.


Assuntos
Vespas , Aminoácidos , Animais , Larva , Néctar de Plantas , Prolina , Vespas/fisiologia , beta-Alanina/farmacologia , Ácido gama-Aminobutírico
2.
J Phys Chem Lett ; 13(9): 2237-2244, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35238571

RESUMO

Extremophiles produce macromolecules which inhibit ice recrystallization, but there is increasing interest in discovering and developing small molecules that can modulate ice growth. Realizing their potential requires an understanding of how these molecules function at the atomistic level. Here, we report the discovery that the amino acid l-α-alanine demonstrates ice recrystallization inhibition (IRI) activity, functioning at 100 mM (∼10 mg/mL). We combined experimental assays with molecular simulations to investigate this IRI agent, drawing comparison to ß-alanine, an isomer of l-α-alanine which displays no IRI activity. We found that the difference in the IRI activity of these molecules does not originate from their ice binding affinity, but from their capacity to (not) become overgrown, dictated by the degree of structural (in)compatibility within the growing ice lattice. These findings shed new light on the microscopic mechanisms of small molecule cryoprotectants, particularly in terms of their molecular structure and overgrowth by ice.


Assuntos
Aminoácidos , Gelo , Proteínas Anticongelantes/metabolismo , Crioprotetores , Cristalização , beta-Alanina
3.
Poult Sci ; 101(5): 101776, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35303689

RESUMO

Carnosine enrichment of slow-growing Korat chicken (KRC) meat helps differentiate KRC from mainstream chicken. We aimed to investigate the effects of ß-alanine and L-histidine supplementation on the carnosine synthesis in and quality and secondary structure of proteins in slow-growing KRC meat. Four hundred 21-day-old female KRC were used, and a completely randomized design was applied. The chickens were divided into 4 experimental groups: basal diet (A), basal diet supplemented with 1.0% ß-alanine (B), 0.5% L-histidine (C), and 1.0% ß-alanine combined with 0.5% L-histidine (D). Each group consisted of 5 replicates (20 chickens per replicate). On d 70, 2 chickens per replicate were slaughtered, and the levels of carnosine, anserine, and thiobarbituric acid reactive substances were analyzed. Biochemical changes were monitored using synchrotron radiation-based Fourier transform infrared microspectroscopy; 5 chickens per replicate were slaughtered, and the meat quality was analyzed. Statistical analysis was performed using ANOVA and principal component analysis (PCA). Group D chickens exhibited the highest carnosine meat content, followed by those in groups B and C. However, amino acid supplementation did not affect anserine content and growth performance. Higher carnosine levels correlated with increasing pH45 min and decreasing drip loss, cooking loss, shear force, and lipid oxidation. PCA revealed that supplementation with only ß-alanine or L-histidine was related to increased content of ß-sheets, ß-turns, and aliphatic bending groups and decreased content of α-helix groups. This study is the first to report such findings in slow-growing chicken. Our findings suggest that KRC can synthesize the highest carnosine levels after both ß-alanine and L-histidine supplementation. Higher carnosine contents do not adversely affect meat quality, improve meat texture, and alter the secondary structures of proteins. The molecular mechanism underlying carnosine synthesis in chickens needs further study to better understand and reveal markers that facilitate the development of nutrient selection programs.


Assuntos
Carnosina , Animais , Anserina/análise , Carnosina/análise , Galinhas , Suplementos Nutricionais , Feminino , Histidina/metabolismo , Carne/análise , Músculo Esquelético/química , beta-Alanina/metabolismo
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 273: 120943, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35183855

RESUMO

Fluorogenic chemosensors using pyridoxal derivatized ligands as fluorophore is a rapidly growing field of research. Here we report a new Fe(III) complex, [Fe(HBala-pydx)(Bala-pydx)] (H2Bala-pydx is the Schiff base of pyridoxal with beta-alanine), which can serve as a sensitive and selective turn-on fluorescent sensor for the detection of cyanide(CN-) in micromolar concentrations (L.O.D. is 1.134 µM), via the ligand displacement approach, in aqueous-acetonitrile medium. The Fe(III) complex is adequately characterized by analytical and spectroscopic methods along with X-ray crystal structure determination.


Assuntos
Cianetos , Bases de Schiff , Cianetos/química , Compostos Férricos , Piridoxal , beta-Alanina
5.
Int J Mol Sci ; 23(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35162943

RESUMO

Uncoupling proteins (UCPs) form a distinct subfamily of the mitochondrial carrier family (MCF) SLC25. Four UCPs, DmUCP4A-C and DmUCP5, have been identified in Drosophila melanogaster on the basis of their sequence homology with mammalian UCP4 and UCP5. In a Parkinson's disease model, DmUCP4A showed a protective role against mitochondrial dysfunction, by increasing mitochondrial membrane potential and ATP synthesis. To date, DmUCP4A is still an orphan of a biochemical function, although its possible involvement in mitochondrial uncoupling has been ruled out. Here, we show that DmUCP4A expressed in bacteria and reconstituted in phospholipid vesicles catalyzes a unidirectional transport of aspartate, which is saturable and inhibited by mercurials and other mitochondrial carrier inhibitors to various degrees. Swelling experiments carried out in yeast mitochondria have demonstrated that the unidirectional transport of aspartate catalyzed by DmUCP4 is not proton-coupled. The biochemical function of DmUCP4A has been further confirmed in a yeast cell model, in which growth has required an efflux of aspartate from mitochondria. Notably, DmUCP4A is the first UCP4 homolog from any species to be biochemically characterized. In Drosophila melanogaster, DmUCP4A could be involved in the transport of aspartate from mitochondria to the cytosol, in which it could be used for protein and nucleotide synthesis, as well as in the biosynthesis of ß-alanine and N-acetylaspartate, which play key roles in signal transmission in the central nervous system.


Assuntos
Ácido Aspártico/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Desacoplamento Mitocondrial/genética , Proteínas de Desacoplamento Mitocondrial/metabolismo , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/biossíntese , Transporte Biológico Ativo , Clonagem Molecular , Citosol/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Mitocôndrias/metabolismo , beta-Alanina/biossíntese
6.
Bioprocess Biosyst Eng ; 45(5): 843-854, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35175424

RESUMO

High-yielding chemical and chemo-enzymatic methods of D-pantothenic acid (DPA) synthesis are limited by using poisonous chemicals and DL-pantolactone racemic mixture formation. Alternatively, the safe microbial fermentative route of DPA production was found promising but suffered from low productivity and precursor supplementation. In this study, Bacillus megaterium was metabolically engineered to produce DPA without precursor supplementation. In order to provide a higher supply of precursor D-pantoic acid, key genes involved in its synthesis are overexpressed, resulting strain was produced 0.53 ± 0.08 g/L DPA was attained in shake flasks. Cofactor CH2-THF was found to be vital for DPA biosynthesis and was regenerated through the serine-glycine degradation pathway. Enhanced supply of another precursor, ß-alanine was achieved by codon optimization and dosing of the limiting L-asparate-1-decarboxylase (ADC). Co-expression of Pantoate-ß-alanine ligase, ADC, phosphoenolpyruvate carboxylase, aspartate aminotransferase and aspartate ammonia-lyase enhanced DPA concentration to 2.56 ± 0.05 g/L at shake flasks level. Fed-batch fermentation in a bioreactor with and without the supplementation of ß-alanine increased DPA concentration to 19.52 ± 0.26 and 4.78 ± 0.53 g/L, respectively. This present study successfully demonstrated a rational approach combining precursor supply engineering with cofactor regeneration for the enhancement of DPA titer in recombinant B. megaterium.


Assuntos
Bacillus megaterium , Bacillus megaterium/genética , Bacillus megaterium/metabolismo , Fermentação , Engenharia Metabólica/métodos , Ácido Pantotênico/genética , Ácido Pantotênico/metabolismo , beta-Alanina/genética , beta-Alanina/metabolismo
7.
Cornea ; 41(2): 243-248, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35037906

RESUMO

ABSTRACT: The Rho kinase inhibitor netarsudil is a recently approved therapeutic option for the management of increased intraocular pressure in the United States. Although phase 3 clinical trials noted corneal changes related to the medication-namely, nonvisually-significant corneal verticillata-descriptions of a unique form of cystic epithelial edema began to surface as netarsudil (and its sister drug ripasudil, approved in Japan) gained widespread use. This series adds 3 new cases and reviews the current literature on this unique side effect.


Assuntos
Benzoatos/efeitos adversos , Edema da Córnea/induzido quimicamente , Epitélio Corneano/patologia , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Benzoatos/uso terapêutico , Edema da Córnea/diagnóstico , Epitélio Corneano/efeitos dos fármacos , Humanos , Hipertensão Ocular/enzimologia , Hipertensão Ocular/fisiopatologia , Estudos Retrospectivos , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêutico
8.
Invest Ophthalmol Vis Sci ; 63(1): 4, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34982146

RESUMO

Purpose: Netarsudil, a Rho kinase inhibitor with norepinephrine transport inhibitory effect, lowers intraocular pressure, however, its effect on axon damage remains to be elucidated. The aim of the current study was to investigate the effect of netarsudil on TNF-induced axon loss and to examine whether it affects phosphorylated-AMP-activated kinase (p-AMPK) and autophagy in the optic nerve. Methods: Intravitreal administration of TNF or TNF with netarsudil was carried out on rats and quantification of axon number was determined. Electron microscopy determined autophagosome numbers. Localization of p-AMPK expression was examined by immunohistochemistry. The changes in p62, LC3-II, and p-AMPK levels were estimated in the optic nerve by immunoblot analysis. The effect of an AMPK activator A769662 or an AMPK inhibitor dorsomorphin on axon number was evaluated. Results: Morphometric analysis revealed apparent protection by netarsudil against TNF-induced axon degeneration. Netarsudil increased autophagosome numbers inside axons. Netarsudil treatment significantly upregulated optic nerve LC3-II levels in both the TNF-treated eyes and the control eyes. Increased p62 protein level induced by TNF was significantly ameliorated by netarsudil. The netarsudil administration alone lessened p62 levels. Netarsudil significantly upregulated the optic nerve p-AMPK levels. A769662 exhibited obvious axonal protection against TNF-induced damage. A769662 treatment upregulated LC3-II levels and the increment of p62 level induced by TNF was significantly ameliorated by A769662. Immunohistochemical analysis revealed that p-AMPK is present in axons. Netarsudil-mediated axonal protection was significantly suppressed by dorsomorphin administration. Conclusions: Netarsudil upregulated p-AMPK and autophagy. Netarsudil-mediated axonal protection may be associated with upregulated p-AMPK.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/fisiologia , Axônios/efeitos dos fármacos , Benzoatos/farmacologia , Degeneração Neural/prevenção & controle , Nervo Óptico/efeitos dos fármacos , Fator de Necrose Tumoral alfa/toxicidade , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Axônios/enzimologia , Axônios/patologia , Compostos de Bifenilo/farmacologia , Inibidores Enzimáticos/farmacologia , Imuno-Histoquímica , Injeções Intravítreas , Masculino , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/metabolismo , Degeneração Neural/enzimologia , Nervo Óptico/ultraestrutura , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Pironas/farmacologia , Ratos , Ratos Wistar , Proteína Sequestossoma-1/metabolismo , Tiofenos/farmacologia , beta-Alanina/farmacologia
9.
Appl Biochem Biotechnol ; 194(4): 1740-1754, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997447

RESUMO

3-Aminopropionic acid (3-APA) has wide applications in food, cosmetics, pharmaceuticals, chemical, and polymer industries. This present study aimed to develop an eco-friendly whole-cell biocatalytic process for the bio-production of 3-APA from fumaric acid (FA) using Bacillus megaterium. A dual-enzyme cascade route with aspartate-1-decarboxylases (ADC) from Bacillus subtilis and native aspartate ammonia-lyase (AspA) was developed. Divergent catalytic efficiencies between these two enzymes led to an imbalance between both enzyme reactions. In order to coordinate AspA and ADC expression levels, gene mining, optimization, and duplication strategies were employed. Additionally, culture cultivation conditions and biocatalysis process parameters were optimized. A maximum 3-APA titer was obtained (11.68 ± 0.26 g/L) with a yield of 0.78 g/g under the following optimal conditions: 45 °C, pH 6.0, and 15 g/L FA. This study established a biocatalysis process for the production of 3-APA from FA using the whole cells of the recombinant B. megaterium.


Assuntos
Aspartato Amônia-Liase , Bacillus megaterium , Bacillus megaterium/genética , Bacillus megaterium/metabolismo , Escherichia coli/genética , Fumaratos , beta-Alanina
10.
Optom Vis Sci ; 99(4): 400-404, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35001067

RESUMO

SIGNIFICANCE: Intracorneal hemorrhages are a rare finding generally associated with surgery or trauma. There is no consensus on preferred management except eliminating or addressing the causative mechanism in hopes of reducing the risk of corneal haze or scarring. PURPOSE: This case highlights a rare adverse outcome of intracorneal hemorrhages occurring after recent initiation of netarsudil, possibly exacerbated by scleral contact lens wear in a patient with open-angle glaucoma and limbal stem cell deficiency. CASE REPORT: A 77-year-old man using scleral contact lenses for therapeutic management of limbal stem cell deficiency started netarsudil for open-angle glaucoma. During an annual follow-up to adjust his scleral contact lenses, the patient developed peripheral intracorneal hemorrhages bilaterally. The intracorneal hemorrhages resolved over the course of 10 weeks after minor adjustments were made to the scleral contact lens fit and netasurdil was discontinued. Visual acuity and intraocular pressure remained stable throughout. CONCLUSIONS: There are few reports of intracorneal hemorrhages associated with scleral contact lens use and even fewer associated with the use of netarsudil. This case proposes several possible causes of the intracorneal hemorrhages, including topical rho-associated kinase inhibitors, contact lens wear, and trauma. Further studies are needed to determine if netarsudil is associated with intracorneal hemorrhages, to understand the sequelae of intracorneal hemorrhages in netarsudil therapy, and to recommend management when intracorneal hemorrhages manifest with netarsudil use.


Assuntos
Lentes de Contato , Glaucoma de Ângulo Aberto , Idoso , Benzoatos , Hemorragia , Humanos , Masculino , Esclera , beta-Alanina/análogos & derivados
11.
J Sci Food Agric ; 102(6): 2553-2562, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34687471

RESUMO

BACKGROUND: ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP) is a physiological indicator in response to drying soil. However, how abscisic acid (ABA) modulates ß-ODAP accumulation and its related agronomic characteristics in drought stressed grass pea (Lathyrus sativus L.) continue to be unclear. The present study aimed to evaluate the effects of ABA addition on drought tolerance, agronomic characteristics and ß-ODAP content in grass pea under drought stress. RESULTS: Exogenous ABA significantly promoted ABA levels by 19.3% and 18.3% under moderate and severe drought stress, respectively, compared to CK (without ABA, used as control check treatment). ABA addition activated earlier trigger of non-hydraulic root-sourced signal at 69.1% field capacity (FC) (65.5% FC in CK) and accordingly prolonged its operation period to 45.6% FC (49.0% FC in CK). This phenomenon was mechanically associated with the physiological mediation of ABA, where its addition significantly promoted the activities of leaf superoxide dismutase, catalase and peroxidase enzymes and the biosynthesis of leaf proline, simultaneously lowering the accumulation of malondialdehyde and hydrogen peroxide under moderate and severe stresses. Interestingly, ABA application significantly increased seed ß-ODAP content by 21.7% and 21.3% under moderate and severe drought stress, but did not change leaf ß-ODAP content. Furthermore, ABA application produced similar shoot biomass and grain yield as control groups. CONCLUSION: Exogenous ABA improved the drought adaptability of grass pea and promoted the synthesis of ß-ODAP in seeds but not in leaves. Our findings provide novel insights into the agronomic role of ABA in relation to ß-ODAP enrichment in grass pea subjected to drought stress. © 2021 Society of Chemical Industry.


Assuntos
Lathyrus , Ácido Abscísico , Aclimatação , Diamino Aminoácidos , Secas , Lathyrus/química , Ervilhas , beta-Alanina/análogos & derivados
12.
Graefes Arch Clin Exp Ophthalmol ; 260(3): 967-974, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34550421

RESUMO

PURPOSE: To evaluate the efficacy and safety profile of netarsudil 0.02% ophthalmic solution in a tertiary glaucoma referral center. METHODS: This retrospective cohort study included patients with glaucoma initiated on netarsudil 0.02% at a single institution from November 2017 to September 2018. Demographic and clinical data were collected, including intraocular pressure (IOP) and drug side effects at baseline and 1-, 3-, and 6-month follow-up visits. RESULTS: A total of 340 eyes of 233 patients were included; mean ± SD patient age was 69.1 ± 12.5 years. One hundred twenty (48%) eyes experienced ≥ 20% decreases in IOP at the 1-month study visit; this effect was maintained through the 6-month visit. IOP-lowering effects in patients using ≥ 3 topical glaucoma medications were similar (all p > 0.1). Eighteen (7.4%) and 7 (2.9%) patients experienced increases in IOP of ≥ 3 and ≥ 5 mmHg, respectively. Across all study visits, conjunctival hyperemia was noted at a rate of 27.6%, and though frequently reported, complaints of blurred vision (31.1%) did not manifest in significant worsening of visual acuity. The rate of drug discontinuation due to insufficient IOP-lowering and side effects was 15.6% and 24.8%, respectively. Twenty-nine (11.4%) and 82 (32.3%) eyes required additional medical and surgical/laser intervention, respectively. CONCLUSION: Commonly used as the last-line medical therapy in this case series, netarsudil safely and significantly reduced IOP in patients with glaucoma, even in those using ≥ 3 glaucoma medications. Increases in IOP of ≥ 3 mmHg occurred in a small number of patients. Subjective vision changes and conjunctival hyperemia were the most frequently reported side effects.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Idoso , Idoso de 80 Anos ou mais , Benzoatos , Glaucoma/tratamento farmacológico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas , Estudos Retrospectivos , Resultado do Tratamento , beta-Alanina/análogos & derivados
13.
J Glaucoma ; 31(1): 60-63, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34731868

RESUMO

PURPOSE: The purpose of this study was to describe anterior subcapsular cataract development in patients on long-term topical netarsudil use. PATIENTS AND METHODS: This clinical observational study summarizes a similar cataract pattern demonstrated in a series of patients from a single physician practice and a university-based outpatient clinic during their routine clinical follow-up visits from October 2020 to August 2021. All patients have been using topical netarsudil once daily for at least 15 months. No anterior capsular changes have been observed in any patient at the time when netarsudil was initiated. RESULTS: Five eyes from 4 patients between the ages of 41 and 61 and 1 eye from a patient aged 84 were found to develop anterior subcapsular opacities 15 to 37 months after beginning netarsudil. These cataracts were overall small, 1 to 3 mm, round, oval or ring-shaped, central or paracentral with mild density. No other risk factors for cataract development apart from age were found in these patients. CONCLUSION: Patients on long-term netarsudil should be monitored for potential development of anterior subcapsular cataracts.


Assuntos
Catarata , Glaucoma , Benzoatos , Catarata/induzido quimicamente , Humanos , Pressão Intraocular , beta-Alanina/análogos & derivados
14.
Chemosphere ; 291(Pt 2): 132955, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34801571

RESUMO

Benfuracarb (BEN), a broad-spectrum carbamate insecticide used for crop protection, is considered toxic to humans and aquatic organisms. However, the potential risk level of BEN to aquatic organisms is still unclear. In this study, we exposed zebrafish embryos to BEN (0.08, 0.49, and 0.90 mg/L) from 3 to 96 hours post-fertilization (hpf). The results showed that BEN caused shorter body length in zebrafish larvae. The activity of superoxide dismutase (SOD) was significantly increased after BEN exposure. Furthermore, the transcription levels of marker genes associated with early embryonic development (myoD, nkx2.4b, myh6, and gh) were disrupted after BEN treatment. Taken together, the data indicate that BEN possesses developmental toxicity to zebrafish. The results provide a valuable reference for assessing BEN's potentially harmful effects on aquatic ecosystems.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Benzofuranos , Ecossistema , Embrião não Mamífero/metabolismo , Humanos , Larva , Estresse Oxidativo , Poluentes Químicos da Água/análise , beta-Alanina/análogos & derivados
15.
Eur J Ophthalmol ; 32(1): 322-326, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33653172

RESUMO

PURPOSE: To assess the effectiveness and safety of adjunctive topical netarsudil 0.02% and latanoprostene bunod 0.024% in patients with glaucoma. METHODS: A retrospective, multi-center, cohort study of patients with glaucoma treated with netarsudil 0.02% or latanoprostene bunod from five tertiary care centers. Inclusion criteria included patients with glaucoma treated with either medication as adjunctive therapy. Outcomes included mean absolute intraocular pressure (IOP) reduction and relative IOP reduction from baseline. Adverse reactions and reasons for discontinuation were reported. One-way analysis of variance, Kruskal-Wallis rank sum test, and Mann Whitney U test compared the outcomes. RESULTS: A total of 95 eyes (95 patients) on netarsudil and 41 eyes (41 patients) on latanoprostene bunod were analyzed. Mean duration of use was 54.3 ± 28 days for netarsudil and 82.9 ± 51.2 days for latanoprostene bunod. At the final visit, mean IOP reduction was 3.9 ± 4.6 mmHg (17.5 ± 6.0%) (p < 0.0001) with netarsudil and 2.9 ± 3.7 mmHg (13.6 ± 16.3%) (p < 0.0001) with latanoprostene bunod. IOP lowering did not depend on baseline number of IOP-lowering medications. The most common reason for discontinuation was non-effectiveness in both groups. CONCLUSION: Similar to monotherapy, netarsudil and latanoprostene bunod demonstrated efficacy in lowering IOP when used as adjunctive therapy.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Anti-Hipertensivos/uso terapêutico , Benzoatos , Estudos de Coortes , Glaucoma/tratamento farmacológico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas , Prostaglandinas F Sintéticas , Estudos Retrospectivos , beta-Alanina/análogos & derivados
16.
Chemistry ; 28(6): e202104086, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-34914148

RESUMO

The reaction of ß-propiolactam in the superacidic systems HF/MF5 (M=Sb, As) led to the formation of monoprotonated 3-aminopropanoyl fluoride in the form of [C(O)F(CH2 )2 NH3 ][SbF6 ] and [C(O)F(CH2 )2 NH3 ][AsF6 ]. In the presence of traces of water, the diprotonated species ß-alanine [C(OH)2 (CH2 )2 NH3 ][AsF6 ]2 was synthesized for the first time. All salts were characterized by low-temperature infrared and Raman spectroscopy. Additionally, single-crystal X-ray analyses were conducted in the case of [C(O)F(CH2 )2 NH3 ][SbF6 ] and [C(OH)2 (CH2 )2 NH3 ][AsF6 ]2 . By using SO2 instead of HF as the solvent, the salt [C(OH)2 (CH2 )2 NHSO][SbF6 ]2 was obtained, and single-crystal X-ray analysis of this salt containing a thionylimide moiety was conducted. For the formation of these open-chain compounds, an acyl cationic species as intermediate is assumed, which is formed from N-protonated ß-propiolactam. Quantum chemical calculations at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels of theory were carried out to gain a better understanding of the formation and the structural properties of protonated ß-propiolactam.


Assuntos
Teoria Quântica , Água , beta-Alanina
17.
Molecules ; 26(23)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34885902

RESUMO

(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)2 is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)2-NH2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)2-NH2 and Caf-(KLAKLAK)2-NH2. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLß-AKLß-AK)2-NH2 containing ß-Ala in its structures exhibited good antimicrobial activity against Escherichia coli K12 407 and Bacillus subtilis 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , /farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Descoberta de Drogas , Escherichia coli K12/efeitos dos fármacos , Humanos , Células MCF-7 , Técnicas de Síntese em Fase Sólida , beta-Alanina/análogos & derivados , beta-Alanina/síntese química , beta-Alanina/farmacologia
18.
Mater Sci Eng C Mater Biol Appl ; 131: 112528, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34857307

RESUMO

In skeletal muscle tissue engineering, success has not been achieved yet, since the properties of the tissue cannot be fully mimicked. The aim of this study is to investigate the potential use of poly-3-hydroxybutyrate (P3HB)/poly-ß-alanine (PBA) fibrous tissue scaffolds with piezoelectric properties for skeletal muscle regeneration. Random and aligned P3HB/PBA (5:1) fibrous matrices were prepared by electrospinning with average diameters of 951 ± 153 nm and 891 ± 247 nm, respectively. X-ray diffraction (XRD) analysis showed that PBA reinforcement and aligned orientation of fibers reduced the crystallinity and brittleness of P3HB matrix. While tensile strength and elastic modulus of random fibrous matrices were determined as 3.9 ± 1.0 MPa and 86.2 ± 10.6 MPa, respectively, in the case of aligned fibers they increased to 8.5 ± 1.8 MPa and 378.2 ± 4.2 MPa, respectively. Aligned matrices exhibited a soft and an elastic behaviour with ~70% elongation in similar to the natural tissue. For the first time, d33 piezoelectric modulus of P3HB/PBA matrices were measured as 5 pC/N and 5.3 pC/N, for random and aligned matrices, respectively. Cell culture studies were performed with C2C12 myoblastic cell line. Both of random and aligned P3HB/PBA fibrous matrices supported attachment and proliferation of myoblasts, but cells cultured on aligned fibers formed regular and thick myofibril structures similar to the native muscle tissue. Reverse transcription polymerase chain reaction (RT-qPCR) analysis indicated that MyoD gene was expressed in the cells cultured on both fiber orientation, however, on the aligned fibers significant increase was determined in Myogenin and Myosin Heavy Chain (MHC) gene expressions, which indicate functional tubular structures. The results of RT-qPCR analysis were also supported with immunohistochemistry for myogenic markers. These in vitro studies have shown that piezoelectric P3HB/PBA aligned fibrous scaffolds can successfully mimic skeletal muscle tissue with its superior chemical, morphological, mechanical, and electroactive properties.


Assuntos
Poliésteres , Engenharia Tecidual , Ácido 3-Hidroxibutírico , Proliferação de Células , Hidroxibutiratos , Músculo Esquelético , Regeneração , Tecidos Suporte , beta-Alanina
19.
Int J Mol Sci ; 22(23)2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34884945

RESUMO

Our previous study described stage-specific responses of 'Norin 61' bread wheat to high temperatures from seedling to tillering (GS1), tillering to flowering (GS2), flowering to full maturity stage (GS3), and seedling to full maturity stage (GS1-3). The grain development phase lengthened in GS1 plants; source tissue decreased in GS2 plants; rapid senescence occurred in GS3 plants; all these effects occurred in GS1-3 plants. The present study quantified 69 flag leaf metabolites during early grain development to reveal the effects of stage-specific high-temperature stress and identify markers that predict grain weight. Heat stresses during GS2 and GS3 showed the largest shifts in metabolite contents compared with the control, followed by GS1-3 and GS1. The GS3 plants accumulated nucleosides related to the nucleotide salvage pathway, beta-alanine, and serotonin. Accumulation of these compounds in GS1 plants was significantly lower than in the control, suggesting that the reduction related to the high-temperature priming effect observed in the phenotype (i.e., inhibition of senescence). The GS2 plants accumulated a large quantity of free amino acids, indicating residual effects of the previous high-temperature treatment and recovery from stress. However, levels in GS1-3 plants tended to be close to those in the control, indicating an acclimation response. Beta-alanine, serotonin, tryptophan, proline, and putrescine are potential molecular markers that predict grain weight due to their correlation with agronomic traits.


Assuntos
Biomarcadores/metabolismo , Metabolômica/métodos , Triticum/crescimento & desenvolvimento , Aclimatação , Temperatura Alta , Prolina/metabolismo , Putrescina/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Serotonina/metabolismo , Triticum/metabolismo , Triptofano/metabolismo , beta-Alanina/metabolismo
20.
Biomolecules ; 11(12)2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34944508

RESUMO

The Cl- permeable GABAA receptor is a major contributor to cellular inhibition in the brain. The receptor is normally activated by synaptically-released or ambient GABA but is sensitive to a number of physiological compounds such as ß-alanine, taurine, and neurosteroids that, to various degrees, activate the receptor and modulate responses either to the transmitter or to each other. Here, we describe α1ß2γ2L GABAA receptor activation and modulation by combinations of orthosteric and allosteric activators. The overall goal was to gain insight into how changes in the levels of endogenous agonists modulate receptor activity and influence cellular inhibition. Experimental observations and simulations are described in the framework of a cyclic concerted transition model. We also provide general analytical solutions for the analysis of electrophysiological data collected in the presence of combinations of active compounds.


Assuntos
Agonistas de Receptores de GABA-A/farmacologia , Receptores de GABA-A/metabolismo , Taurina/farmacologia , beta-Alanina/farmacologia , Regulação Alostérica , Animais , Simulação por Computador , Etiocolanolona/farmacologia , Humanos , Pregnanolona/farmacologia
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