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1.
Braz. j. biol ; 84: e250936, 2024. graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1345557

RESUMO

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.


Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.


Assuntos
Animais , Masculino , Ratos , Queimaduras/tratamento farmacológico , Glutamina , Ratos Wistar , Dipeptídeos , Modelos Animais de Doenças , Aminoácidos
3.
Chem Senses ; 472022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35512652

RESUMO

In addition to the well-accepted taste receptors corresponding to the 6 basic taste qualities, sweet, salty, sour, bitter, umami, and fatty, another type of taste receptor, calcium-sensing receptor (CaSR), is located in taste bud cells. CaSR is called the kokumi receptor because its agonists induce koku (or kokumi), a Japanese word meaning the enhancement of flavor characteristics, such as thickness, mouthfulness, and continuity. Kokumi is an important factor in enhancing food palatability. γ-Glu-Val-Gly (EVG) is the most potent agonist of CaSR, which induces a strong kokumi flavor. However, no behavioral studies have been documented in animals using EVG. Here, we show that EVG at low concentrations that do not elicit a taste of its own enhances preferences for umami, fat, and sweet taste solutions in rats. An increased preference for inosine monophosphate (IMP) and Intralipos was the most dominant effect. NPS-2143, an antagonist of CaSR, abolished the additive effect of EVG on IMP and Intralipos solutions. These effects of EVG on taste stimuli are thought to occur in the oral cavity, because the effects of EVG were confirmed in a brief exposure test. The additive effects on IMP and Intralipos remained after the transection of the chorda tympani, indicating that these effects also occur in the palate and/or posterior part of the tongue. Moreover, the additive effects of EVG were verified in electrophysiological taste nerve responses. These results may partially provide the underlying mechanisms for EVG to induce kokumi flavor in humans.


Assuntos
Papilas Gustativas , Paladar , Animais , Suplementos Nutricionais , Dipeptídeos , Ingestão de Alimentos , Inosina Monofosfato/farmacologia , Ratos , Receptores de Detecção de Cálcio , Paladar/fisiologia
4.
Carbohydr Res ; 514: 108546, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35364384

RESUMO

New, simple, synthetic routes for the preparation of novel glycopeptide antibiotics are described. The structures of the synthesized compounds are elucidated by IR, two-dimensional NMR spectroscopy, and mass spectrometry. The stability of the new glycopeptide derivatives 10a,b is confirmed by assessing the physical character, HOMO-LUMO gap energy, ESP, and the corresponding correlation of 2D-NMR analysis. Furtherly, the target precursors are investigated via the DFT/B3LYP/6-311(G) basis set.


Assuntos
Antibacterianos , Glicopeptídeos , Dipeptídeos , Glicosilação , Espectroscopia de Ressonância Magnética/métodos
5.
Sci Rep ; 12(1): 5644, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379876

RESUMO

Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these mice, including mild motor neuron loss, but no TDP-43 mis-localization, as well as motor and cognitive impairments. We suggest that this model can serve as the foundation for phenotypic exacerbation through second-hit forms of stress.


Assuntos
Esclerose Amiotrófica Lateral , Demência Frontotemporal , Esclerose Amiotrófica Lateral/metabolismo , Animais , Arginina/genética , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Dipeptídeos/metabolismo , Feminino , Demência Frontotemporal/patologia , Glicina/genética , Masculino , Camundongos , Fenótipo
6.
Carbohydr Polym ; 287: 119304, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35422283

RESUMO

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects women of reproductive age. Resistant starch can be fermented by gut microbes then produce short-chain fatty acids (SCFAs). It was reported SCFAs might play a key role in gut microbiota-dependent therapy of PCOS. However, the effects of resistant starch on PCOS symptoms have not yet been investigated. Here, maize starch was acylated with specific SCFAs. Our results indicated that acylated starch can release acetate, propionate, and butyrate into the caecum and colon. Treatment with butylated starch (BS) alleviated abnormal ovarian morphology, metabolic disorders, and sex hormone imbalance in letrozole-treated rats, whereas treatment with acetylated starch and propylated starch did not exhibit such effects. Furthermore, BS stimulated the secretion of peptide tyrosine-tyrosine into the serum by activating a G protein-coupled receptor, GPR41, which further affected disease phenotypes. In addition, compared with caecal microbiota, faecal microbiota was more affected by BS. Butyrate-producing microbes were enriched in faeces after BS treatment and may have helped further to relieve PCOS symptoms.


Assuntos
Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Animais , Butiratos/farmacologia , Dipeptídeos , Ácidos Graxos Voláteis/metabolismo , Fezes , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Ratos , Amido Resistente , Amido/farmacologia
7.
Int J Mol Sci ; 23(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35408963

RESUMO

This study evaluates the effects of five different peptides, the Epitalon® tetrapeptide, the Vilon® dipeptide, the Thymogen® dipeptide, the Thymalin® peptide complex, and the Chonluten® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides®), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity.


Assuntos
Lipopolissacarídeos , Monócitos , Citocinas/metabolismo , Dipeptídeos/farmacologia , Células Endoteliais/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Monócitos/metabolismo , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
8.
J Phys Chem B ; 126(16): 2968-2978, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35438499

RESUMO

Dipeptides, the prototype peptides, exist in both linear (l-) and cyclo (c-) structures. Since the first mass spectrometry experiments, it has been observed that some l-structures may turn into the cyclo ones, likely via a temperature-induced process. In this work, combining several different experimental techniques (mass spectrometry, infrared and Raman spectroscopy, and thermogravimetric analysis) with tight-binding and ab initio simulations, we provide evidence that, in the case of l-phenylalanyl-l-alanine, an irreversible cyclization mechanism, catalyzed by water and driven by temperature, occurs in the condensed phase. This process can be considered as a very efficient strategy to improve dipeptide stability by turning the comparatively fragile linear structure into the robust and more stable cyclic one. This mechanism may have played a role in prebiotic chemistry and can be further exploited in the preparation of nanomaterials and drugs.


Assuntos
Alanina , Fenilalanina , Alanina/química , Ciclização , Dipeptídeos/química , Peptídeos
9.
Molecules ; 27(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35408669

RESUMO

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine-natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO- (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1-8 were similar. The obtained results in the presence of amides 1-4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.


Assuntos
Hemostáticos , Amidas/farmacologia , Dipeptídeos/farmacologia , Hemólise , Hemostasia , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina
10.
J Chem Phys ; 156(15): 154108, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35459300

RESUMO

A method for obtaining appropriate reaction coordinates is required to identify transition states distinguishing the product and reactant in complex molecular systems. Recently, abundant research has been devoted to obtaining reaction coordinates using artificial neural networks from deep learning literature, where many collective variables are typically utilized in the input layer. However, it is difficult to explain the details of which collective variables contribute to the predicted reaction coordinates owing to the complexity of the nonlinear functions in deep neural networks. To overcome this limitation, we used Explainable Artificial Intelligence (XAI) methods of the Local Interpretable Model-agnostic Explanation (LIME) and the game theory-based framework known as Shapley Additive exPlanations (SHAP). We demonstrated that XAI enables us to obtain the degree of contribution of each collective variable to reaction coordinates that is determined by nonlinear regressions with deep learning for the committor of the alanine dipeptide isomerization in vacuum. In particular, both LIME and SHAP provide important features to the predicted reaction coordinates, which are characterized by appropriate dihedral angles consistent with those previously reported from the committor test analysis. The present study offers an AI-aided framework to explain the appropriate reaction coordinates, which acquires considerable significance when the number of degrees of freedom increases.


Assuntos
Inteligência Artificial , Dipeptídeos , Alanina , Dipeptídeos/química , Isomerismo , Redes Neurais de Computação
11.
Cell Commun Signal ; 20(1): 55, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443669

RESUMO

BACKGROUND: Synapses can adapt to changes in the intracerebral microenvironment by regulation of presynaptic neurotransmitter release and postsynaptic neurotransmitter receptor expression following hypoxic ischemia (HI) injury. The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) exerts a protective effect on neurons after HI and may be involved in maintaining the function of synaptic networks. In this study, we investigated the changes in the expression of NAAG, glutamic acid (Glu) and metabotropic glutamate receptors (mGluRs), as well as the dynamic regulation of neurotransmitters in the brain after HI, and assessed their effects on synaptic plasticity of the cerebral cortex. METHODS: Thirty-six Yorkshire newborn pigs (3-day-old, males, 1.0-1.5 kg) were selected and randomly divided into normal saline (NS) group (n = 18) and glutamate carboxypeptidase II inhibition group (n = 18), both groups were divided into control group, 0-6 h, 6-12 h, 12-24 h, 24-48 h and 48-72 h groups (all n = 3) according to different post-HI time. The content of Glu and NAAG after HI injury were detected by 1H-MRS scanning, immunofluorescence staining of mGluRs, synaptophysin (syph) along with postsynaptic density protein-95 (PSD95) and transmission electron microscopy were performed. ANOVA, Tukey and LSD test were used to compare the differences in metabolite and protein expression levels among subgroups. Correlation analysis was performed using Pearson analysis with a significance level of α = 0.05. RESULTS: We observed that the NAAG and mGluR3 expression levels in the brain increased and then decreased after HI and was significantly higher in the 12-24 h (P < 0.05, Tukey test). There was a significant positive correlation between Glu content and the expression of mGluR1/mGluR5 after HI with r = 0.521 (P = 0.027) and r = 0.477 (P = 0.045), respectively. NAAG content was significantly and positively correlated with the level of mGluR3 expression (r = 0.472, P = 0.048). When hydrolysis of NAAG was inhibited, the expression of synaptic protein PSD95 and syph decreased significantly. CONCLUSIONS: After 12-24 h of HI injury, there was a one-time elevation in NAAG levels, which was consistent with the corresponding mGluR3 receptor expression trend; the NAAG maintains cortical synaptic plasticity and neurotransmitter homeostasis by inhibiting presynaptic glutamate vesicle release, regulating postsynaptic density proteins and postsynaptic receptor expression after pathway activation. Video abstract.


Assuntos
Dipeptídeos , Receptores de Glutamato Metabotrópico , Animais , Córtex Cerebral/metabolismo , Dipeptídeos/metabolismo , Dipeptídeos/farmacologia , Ácido Glutâmico , Isquemia , Masculino , Plasticidade Neuronal/fisiologia , Neurotransmissores/farmacologia , Receptores de Glutamato Metabotrópico/metabolismo , Suínos
12.
J Agric Food Chem ; 70(15): 4591-4598, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35395154

RESUMO

Biotic stresses (fungi, bacteria, insects, weeds, etc.) are some of the most important causes of the decrease in the quality and quantity of crops that could become an emergency due to a noteworthy increase in the world population. Thus, to overcome these problems, massive use of chemical pesticides has been carried out with heavy consequences for environmental pollution and food safety. An eco-friendly alternative can be using natural compound-based biopesticides with high efficacy and selectivity. Some bacterial lipodepsipeptides (tolaasins I, II, A, D, and E and WLIP together with hexacetyl- and tetrahydro-tolaasin I and WLIP methyl ester) and cyclic dipeptides (cyclo(l-Pro-l-Tyr), cyclo(d-Pro-l-Tyr), cyclo(l-Pro-l-Val), and cyclo(l-Pro-l-Leu)) were assayed against several pathogenic bacteria and fungi of important agrarian plants. Lipodepsipeptides showed strong growth inhibition of all microorganisms tested in the range of 0.1-0.8 µg/mL, while cyclodipeptides, despite preserving this ability, showed a noteworthily reduced antimicrobial activity being active only in the range of 15-900 µg/mL. Among the lipodepsipeptides and cyclic dipeptides assayed, tolaasin d and cyclo(l-Pro-l-Tyr) (also named maculosin-1) appeared to be the most toxic compounds. Some structure-activity relationships of lipodepsipeptides were also discussed along with their practical application as biopesticides in agriculture.


Assuntos
Agentes de Controle Biológico , Fungos , Bactérias/genética , Dipeptídeos/química , Dipeptídeos/farmacologia , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Plantas
13.
Mar Drugs ; 20(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35447925

RESUMO

Excessive exposure of the skin to ultraviolet irradiation induces skin photoaging, which seriously deteriorates the barrier functions of skin tissue, and even causes skin damages and diseases. Recently, dietary supplements from marine sources have been found to be useful in modulating skin functions and can be used to alleviate photoaging. Herein, the low-molecular-weight hydrolysates with a photoaging-protection effect were prepared by enzymatic hydrolysis from Theragra chalcogramma (TCH), and the potential mechanism were subsequently explored. The results revealed that TCH desirably improved the barrier functions of photoaged skin and stimulated the deposition of ECM components Col I, Hyp, and HA in the dermal layer. Histologically, TCH reduced the epidermal hyperplasia and restored the impaired architectures in a dose-dependent manner. Meanwhile, the activity of matrix metalloproteinase-1 (MMP-1) in photoaging skin was inhibited, and the expression levels of elastin and fibrillin-1 were elevated accordingly after TCH administration, and the significant improvements were observed at high-dose level (p < 0.05). Taken together, the efficacy of TCH against skin photoaging is highly associated with the regulation on ECM metabolism and the repairing of damaged mechanical structure.


Assuntos
Gadiformes , Envelhecimento da Pele , Animais , Colágeno/metabolismo , Dipeptídeos , Gadiformes/metabolismo , Ratos , Ratos Sprague-Dawley , Pele , Raios Ultravioleta/efeitos adversos
14.
Proc Natl Acad Sci U S A ; 119(11): e2113813119, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35259014

RESUMO

SignificanceThe GGGGCC hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS). Despite myriad studies on the toxic effects of poly-dipeptides produced from the C9orf72 repeats, the mechanisms underlying the selective hyperexcitability of motor cortex that characterizes the early stages of C9orf72 ALS patients remain elusive. Here, we show that the proline-arginine poly-dipeptides cause hyperexcitability in cortical motor neurons by increasing persistent sodium currents conducted by the Nav1.2/ß4 sodium channel complex, which is highly expressed in the motor cortex. These findings provide the basis for understanding how the C9orf72 mutation causes motor neuron hyperactivation that can lead to the motor neuron death in C9orf72 ALS.


Assuntos
Esclerose Amiotrófica Lateral/etiologia , Esclerose Amiotrófica Lateral/metabolismo , Proteína C9orf72/genética , Dipeptídeos/genética , Hipercinese/genética , Neurônios Motores/metabolismo , Esclerose Amiotrófica Lateral/patologia , Arginina , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Dipeptídeos/metabolismo , Suscetibilidade a Doenças , Potencial Evocado Motor , Predisposição Genética para Doença , Humanos , Fenótipo , Prolina , Sódio/metabolismo
15.
Phys Chem Chem Phys ; 24(13): 8022-8031, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35315463

RESUMO

We report on the properties of the thin films of the short peptide L-dialanine grown on Cu(100) surfaces and compare them to those of L-alanine by using surface techniques like XPS, IRRAS and STM. The first dialanine monolayer, in contact with the metallic substrate, is found to consist of whole neutral molecules in the non-zwitterionic state forming a c(2 × 4) pattern with quasi-hexagonal symmetry. The peptide bond of dialanine is preserved in the adsorption state. The ordering of the L-dialanine overlayer is shown to replicate rearrangements of the atoms of the substrate around dislocations of the latter indicating a strong molecule-surface interaction. In the multilayer regime, molecules of the second and further layers are found to be in a zwitterionic state, readily desorbing even at room temperature. The first dialanine layer is tightly bound to the substrate, begins to desorb at temperatures higher than 390 K and cracks down at the surface, transforming into a new moiety, beyond 435 K.


Assuntos
Alanina , Dipeptídeos , Adsorção , Dipeptídeos/química , Temperatura
16.
Medicina (Kaunas) ; 58(3)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35334570

RESUMO

Background and Objectives: Diarrhea induced by chemotherapy may represent a life-threatening adverse effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity, particularly with higher doses. Management of diarrhea is crucial to increase the survival of cancer patients and to improve the quality of life. Glutamine is an abundant protein peptide found in blood and has a crucial role in boosting immunity, increasing protein anabolism, and decreasing the inflammatory effects of chemotherapy on the mucosal membranes, including diarrhea. This study aimed to provide evidence that parenteral L-alanyl L-glutamine dipeptide may have a positive influence on the incidence of diarrhea, treatment response, and the overall survival in colon cancer patients treated with modified FOLFOX-6 (mFOLFOX-6). Materials and Methods: Forty-four stage II and III colon cancer patients were included in this study where they were treated with the standard colon cancer chemotherapy mFOLFOX-6 and were randomly allocated into glutamine group and placebo group, each of 22 patients. Results: L-alanyl L-glutamine dipeptide was found to be significantly effective in decreasing the frequency and severity of diarrhea when compared to the placebo group, particularly after four and six cycles of mFOLFOX-6. There was no significant difference between the studied groups regarding to the overall survival. Conclusion: L-alanyl L-glutamine dipeptide can be considered as an add-on with chemotherapy to improve the quality of life and the overall survival of colon cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo , Glutamina , Neoplasias do Colo/tratamento farmacológico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Fluoruracila/uso terapêutico , Glutamina/farmacologia , Humanos , Incidência , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Qualidade de Vida
17.
Prostate ; 82(7): 826-835, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35286735

RESUMO

BACKGROUND: An updated systematic review and meta-analysis of relevant studies to evaluate the effectiveness of prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) in castration resistant prostate cancer (CRPC). METHODS: A systematic search was performed in July 2020 using PubMed/Medline database to update our prior systematic review. The search was limited to papers published from 2019 to June 2020. A total of 472 papers were reviewed. The studied parameters included pooled proportion of patients showing any or ≥50% prostate-specific antigen (PSA) decline after PRLT. Survival effects of PRLT were assessed based on pooled hazard ratios (HRs) of the overall survival (OS) according to any PSA as well as ≥50% PSA decline after PRLT. Response to therapy based on ≥50% PSA decrease after PRLT versus controls was evaluated using Mantel-Haenszel random effect meta-analysis. All p values < 0.05 were considered as statistically significant. RESULTS: A total of 45 publications were added to the prior 24 studies. 69 papers with total of 4157 patients were included for meta-analysis. Meta-analysis of the two recent randomized controlled trials showed that patients treated with 177 Lu-PSMA 617 had a significantly higher response to therapy compared to controls based on ≥50% PSA decrease. Meta-analysis of the HRs of OS according to any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. CONCLUSIONS: PRLT results in higher proportion of patients responding to therapy based on ≥50% PSA decline compared to controls. Any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. ADVANCES IN KNOWLEDGE: This is the first meta-analysis to aggregate the recent randomized controlled trials of PRLT which shows CRPC patients had a higher response to therapy after PRLT compared to controls.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio/uso terapêutico , Masculino , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
18.
Bull Exp Biol Med ; 172(5): 579-582, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35352249

RESUMO

Metabolism of a new neuroprotector GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester) in rat blood plasma was studied by HPLC-mass spectrometry. Four biotransformation products were identified. It is concluded that the main ways of GZK-111 biotransformation are hydrolysis of the ester bond by esterases followed by degradation of the resulting metabolite, as well as reactions leading to the formation of phenylacetic acid and cycloprolylglycine that exhibits neuropsychotropic activity.


Assuntos
Dipeptídeos , Fármacos Neuroprotetores , Animais , Biotransformação , Cromatografia Líquida de Alta Pressão , Dipeptídeos/farmacologia , Hidrólise , Espectrometria de Massas , Fármacos Neuroprotetores/farmacologia , Ratos
19.
Int J Mol Sci ; 23(6)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35328611

RESUMO

Short peptides have been spiking interest owing to their significant contribution to the taste and functional properties of dry-cured ham. In this study, a suspect screening approach based on high-resolution mass spectrometry was employed for the comprehensive characterization of the short endogenous peptidome in dry-cured ham samples at different processing stages (14, 22, and 34 months). After careful manual spectra interpretation, a chemometric approach based on principal component analysis was employed for highlighting the differences between the three sets of samples. A total of 236 short peptide sequences was tentatively identified, including 173 natural short peptides and 63 sequences containing non-proteinogenic amino acids, the highest number ever reported for endogenous sequences in dry-cured ham. Samples in the latest processing stages presented a generally higher abundance of dipeptides, indicating residual proteolytic activity. Moreover, the several annotated modified short peptides, mainly pyroglutamination and lactoyl conjugation, allowed hypothesizing several reactions occurring over time. For the first time, several lactoyl-dipeptides were tentatively identified in dry-cured ham samples with maximum concentration in the late processing stage samples. The presented results significantly contribute to the understanding of the reaction involving short peptides that affect the sensory and functional properties of dry-cured ham.


Assuntos
Produtos da Carne , Carne de Porco , Dipeptídeos , Manipulação de Alimentos/métodos , Espectrometria de Massas/métodos , Peptídeos/química
20.
Int J Mol Sci ; 23(6)2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35328756

RESUMO

The three-dimensional structure of tyrosinase has been crystallized from many species but not from Homo sapiens. Tyrosinase is a key enzyme in melanin biosynthesis, being an important target for melanoma and skin-whitening cosmetics. Several studies employed the structure of tyrosinase from Agaricus bisporus as a model enzyme. Recently, 98% of human genome proteins were elucidated by AlphaFold. Herein, the AlphaFold structure of human tyrosinase and the previous model were compared. Moreover, tyrosinase-related proteins 1 and 2 were included, along with inhibition studies employing kojic and cinnamic acids. Peptides are widely studied for their inhibitory activity of skin-related enzymes. Cyanophycin is an amino acid polymer produced by cyanobacteria and is built of aspartic acid and arginine; arginine can be also replaced by other amino acids. A new set of cyanophycin-derived dipeptides was evaluated as potential inhibitors. Aspartate-glutamate showed the strongest interaction and was chosen as a leading compound for future studies.


Assuntos
Dipeptídeos , Monofenol Mono-Oxigenase , Arginina , Proteínas de Bactérias , Dipeptídeos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/metabolismo
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