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1.
J Drug Target ; : 1-15, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38980282

ABSTRACT

Cost-effective strategies for the treatment of chronic wounds must be developed. The green synthesis of gold nanoparticles (GNPs) it is possible to guarantee a lower toxicity in biological tissues and greater safety of applicability, in addition to adding the effects of nanoparticles (NPs) to those of extracts. The objective of this study was to evaluate the effects of treatment with biosynthesized GNPs in a chronic wound model. Wistar rats were distributed into 7 groups: Acute Wound (AW); Chronic wound (CW); CW + GNPs-Açaí; CW + GNPs-DB; CW + AV-GNPs; CW + SafGel®; CW + 660 nm laser. The chronic injury model was induced with topically applied Resiquimod for 6 days. Treatments were then initated on the fourteenth day after the last application of Resiquimod and carried out daily for ten days. The proposed therapies with GNPs were able to significantly reduce the inflammatory score and increase the rate of wound contraction. In histology, there was a reduction in the inflammatory infiltrate and increased gene expression of fibronectin and type III collagen, mainly in the CW + AV-GNPs group. The therapies were able to reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and reduce oxidative stress. The results demonstrated that the effects of GNPs appear to complement those of the extracts, thereby enhancing the tissue repair process.

2.
AIDS Behav ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992229

ABSTRACT

This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7-12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-É£, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.

3.
J Eval Clin Pract ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38993004

ABSTRACT

BACKGROUND: Tackling client absenteeism in primary and secondary care settings is crucial to ensure the continuity of care for individuals, families and communities, as well as preventing waste of resources within healthcare systems. METHODOLOGY: This article is an integrative review to identify advancements in health technologies that address client absenteeism in primary and secondary care. The databases Medical Literature and Retrieval System Online (MEDLINE/PubMed®), Scientific Electronic Library Online and Virtual Health Library were consulted. The inclusion criteria were as follows: full papers, published between 2013 and 2023, in English, Portuguese or Spanish. The descriptors used were the following: patients, mobile applications, health services management, absenteeism and primary care, and secondary care. Eleven articles published from 2014 to 2021 were included. RESULTS: Most articles were identified in the MEDLINE/PUBMED database, employed a randomized controlled trial methodology (36.36%), and were published between 2019 and 2021 (90.0%) in English (63.7%). The applications had managerial, assistive and/or educational purposes. In addition to absenteeism control, these applications strived to promote client engagement with health services, increase health literacy and tackle structural barriers to care, such as language barriers. CONCLUSION: Efforts are needed to ensure that providers receive training to educate clients on the applications. Moreover, community-based participatory studies to ensure the feasibility of applications are warranted.

4.
Front Med (Lausanne) ; 11: 1408290, 2024.
Article in English | MEDLINE | ID: mdl-38933108

ABSTRACT

Background: Epstein-Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients. Methods: We recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO. Results: The DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection. Conclusion: Our results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

5.
Orthod Craniofac Res ; 27(2): 185-192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37786950

ABSTRACT

Rapid maxillary expansion (RME) may change speech sound parameters due to the enlargement of oral and nasal cavities. This study aimed to systematically review the current evidence on speech changes as a side effect of RME. An electronic search was conducted in nine databases, and two of them accessed the 'grey literature'. The eligibility criteria included clinical studies assessing orthodontic patients with maxillary transverse deficiency and the relationship with speech alterations without restricting publication year or language. Only interventional studies were included. The JBI Critical Appraisal Tool assessed the risk of bias. The initial search provided 4853 studies. Seven articles (n = 200 patients) met the inclusion criteria and were analysed. The primary source of bias was the absence of a control group in four studies. RME altered speech production by changing vowel fundamental frequency and fricative phoneme formant frequency. Shimmer and jitter rates changed in one and two studies, respectively. Two studies presented deterioration during orthodontic treatment, but speech improved after appliance removal. Despite the limited evidence, RME affects speech during and after treatment.


Subject(s)
Palatal Expansion Technique , Phonetics , Humans , Palatal Expansion Technique/adverse effects , Speech , Maxilla , Nasal Cavity
6.
Anal Methods ; 15(38): 5078-5086, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37743828

ABSTRACT

The expansion of monocultures to regions close to conservation areas has put biodiversity at risk, mainly due to the intense use of pesticides. Anurans are highly susceptible to pesticides and may be a biological marker in the contamination of an area. However, methods for determining pesticides in anurans are incipient. In this work, a miniaturized QuEChERS method was developed for the extraction of atrazine, chlorpyrifos, α- and ß-endosulfan, α-, ß-, θ- and ζ-cypermethrin in anuran adipose tissues. The method was optimized for the tissue sample size scale according to sample mass availability. Extracting solvent and adsorbents for the clean-up step was evaluated, achieving recoveries next to 100% with acetonitrile and without a clean-up step. The mini-QuEChERS method, using 500 mg of adipose tissue, 50 mg of NaCl and 200 mg of MgSO4, 100 µL of ultrapure water, and 1.50 mL of acetonitrile with no purification step, followed by high-performance liquid chromatography analysis and photodiode array detection was validated following the European Community guidelines. The methodology showed a moderate matrix effect for some pesticides, which was corrected using the matrix-matched calibration. The limits of quantification for the pesticide residues in adipose tissues ranged from 10 to 75 µg kg-1. Pesticide recoveries ranged from 74% to 115%, and repeatability and within-lab reproducibility showed relative standard deviations < 11%. The mini-QuEChERS method was applied to extract pesticide residues from the adipose tissues of two species of anurans: Leptodactylus macrosternum and Scinax x-signatus. 25% of samples were positive, detecting endosulfan and chlorpyriphos, confirmed by liquid chromatography coupled to tandem mass spectrometry. The mini-QuEChERS was a simple, economical, and eco-friendly method for extracting pesticide residues in anuran adipose tissue samples.

7.
J Neuroimmune Pharmacol ; 18(3): 235-247, 2023 09.
Article in English | MEDLINE | ID: mdl-37526817

ABSTRACT

Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune neurological disease and is the most common subtype of MS. In addition, it is associated with the development of depression and anxiety. To date, depressive- and anxiety-like behaviours were only studied using models of progressive MS, which causes severe motor alterations. Thus, we sought to standardise the depressive and anxiety-like behaviours in an RRMS model induced by experimental autoimmune encephalomyelitis (RR-EAE) in mice. The RR-EAE model was induced in C57BL/6 female mice using myelin oligodendrocyte glycoprotein (MOG35-55) antigen and Quillaja saponin (Quil A) as an adjuvant. The immunisation of RR-EAE did not induce locomotor alteration but caused relapsing-remitting induction of clinical scores in mice until 35 post-immunization (p.i.). Also, increased levels of tumour necrosis factor alpha (TNF-α), astrocyte marker (GFAP), and microglial markers (IBA-1) were detected in the prefrontal cortex at 35 p.i. of RR-EAE. In the open field test, RR-EAE mice showed decreased time spent at the centre and sniffing behaviour (at days 21 and 34 p.i.). Also, on day 35 p.i. the RR-EAE group spent less time in the open arms and had decreased open-arm entries compared to control mice in the elevated plus maze (EPM) test, confirming the anxiety-like behaviour. At day 36° p.i. in the tail suspension test, mice showed depression-like behaviour with decreased latency time and increased immobility time. Thus, the RR-EAE model mimics the neuroinflammatory and behavioural features of the RRMS, including depression- and anxiety-like symptoms.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Mice , Female , Animals , Depression , Mice, Inbred C57BL , Myelin-Oligodendrocyte Glycoprotein/toxicity , Anxiety , Disease Models, Animal
8.
Antioxidants (Basel) ; 12(8)2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37627569

ABSTRACT

This study aimed to evaluate and compare the effects of treatment with gold nanoparticles (GNPs) reduced with Curcumin (Curcuma longa L.) or Açai (Euterpe oleracea) to a standard commercial treatment of the pharmacological type (Omcilon®) and an electrophysical agent (photobiomodulation) in the palatal wounds of rats. As for the in vitro assay, a cell viability test was performed to assess the toxicity of the synthesized nanoparticles. In vivo assay: 60 Wistar rats were divided into five groups (n = 12): I. Palatal Wound (PW); II. PW + Photobiomodulation (PBM); III. PW + Omcilon®; IV. PW + GNPs-Cur (0.025 mg/mL); V. PW + GNPs-Açai (0.025 mg/mL). Animals were first anesthetized, and circular lesions in the palatine mucosa were induced using a 4 mm-diameter punch. The first treatment session started 24 h after the injury and occurred daily for 5 days. The animals were euthanized, and the palatal mucosa tissue was removed for histological, biochemical, and molecular analysis. GNPs-Açai were able to significantly reduce pro-inflammatory cytokines and increase anti-inflammatory ones, reduce oxidant markers, and reduce inflammatory infiltrate while increasing the collagen area and contraction rate of the wound, along with an improved visual qualification. The present study demonstrated that the proposed therapies of GNPs synthesized greenly, thus associating their effects with those of plants, favor the tissue repair process in palatal wounds.

9.
Preprint in Portuguese | SciELO Preprints | ID: pps-6014

ABSTRACT

Objective: To analyze and identify in the scientific literature how remote teaching is being used and how it was evaluated in postgraduate health courses. Methods: Systematic review with a search in the Virtual Health Library (VHL), with the descriptors distance education, remote learning, residency, graduate studies and health in Portuguese and English, between 2017 and 2021, in Portuguese, English and Spanish. Results: From 750 initial results, 19 articles were included. The United States leads with the largest number of publications on the subject. The evaluation of students who studied through remote teaching is positive. Conclusion: Remote teaching was introduced very quickly for a large number of specialties in the world, with this, even showing positive aspects in this type of teaching, some negative points were evident and that future improvements must be made


Objetivo: Analizar e identificar en la literatura científica el uso de la enseñanza a distancia y su evaluación en los cursos de posgrado en salud. Métodos: Revisión sistemática en las bases de datos Medline, Lilacs, BDEnf, IBECS, BBO y BDENF con los descriptores educación a distancia, aprendizaje a distancia, residencia, estudios de posgrado y salud entre 2017 y 2021, en portugués, inglés y español. Resultados: La búsqueda inicial identificó 750 resultados. En la fase de análisis de títulos y resúmenes quedaron 66 estudios. Finalmente, se incluyeron 19 artículos. Estados Unidos lidera con el mayor número de publicaciones sobre el tema. La valoración de los alumnos que estudiaron a través de la docencia a distancia es positiva. Conclusión: La enseñanza a distancia se implementó muy rápidamente para una gran cantidad de especialidades en el mundo, con lo que, aun mostrando aspectos positivos en este tipo de enseñanza, se evidenciaron algunos puntos negativos y que se deben realizar mejoras futuras


Objetivo: Analisar e identificar na literatura científica a utilização do ensino remoto e sua avaliação em cursos de pós-graduação em saúde. Métodos: Revisão sistemática nas bases de dados Medline, Lilacs, BDEnf, IBECS, BBO e BDENF com os descritores educação a distância, ensino remoto, residência, pós-graduação e saúde entre 2017 a 2021, nos idiomas português, inglês e espanhol. Resultados: A busca inicial identificou 750 resultados. Na fase de análise dos títulos e resumos sobraram 66 estudos. Por fim foram incluídos 19 artigos. Os Estados Unidos lideram com o maior número de publicações acerca do tema. A avaliação dos discentes que estudaram através do ensino remoto é positiva. Conclusão: O ensino remoto foi colocado de forma muito rápida para uma grande quantidade de especialidades no mundo, com isso, mesmo evidenciando-se aspectos positivos nesse tipo de ensino, ficou evidente alguns pontos negativos e que se deve fazer melhorias futuras.

10.
Article in English | MEDLINE | ID: mdl-37047897

ABSTRACT

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.


Subject(s)
COVID-19 , Female , Humans , Male , COVID-19/epidemiology , Cross-Sectional Studies , Liver/metabolism , Liver Function Tests , gamma-Glutamyltransferase , Ferritins , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism
11.
Basic Clin Pharmacol Toxicol ; 132(6): 473-485, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36882317

ABSTRACT

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.


Subject(s)
Curcumin , Metal Nanoparticles , Pneumonia , Rats , Animals , Lipopolysaccharides/toxicity , Rats, Wistar , Gold/pharmacology , Curcumin/pharmacology , Pneumonia/chemically induced , Pneumonia/drug therapy , Pneumonia/prevention & control , Lung/pathology , Cytokines , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Anti-Inflammatory Agents/pharmacology
12.
Nutrients ; 15(5)2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36904195

ABSTRACT

A significant proportion of patients experience a wide range of symptoms following acute coronavirus disease 2019 (COVID-19). Laboratory analyses of long COVID have demonstrated imbalances in metabolic parameters, suggesting that it is one of the many outcomes induced by long COVID. Therefore, this study aimed to illustrate the clinical and laboratory markers related to the course of the disease in patients with long COVID. Participants were selected using a clinical care programme for long COVID in the Amazon region. Clinical and sociodemographic data and glycaemic, lipid, and inflammatory screening markers were collected, and cross-sectionally analysed between the long COVID-19 outcome groups. Of the 215 participants, most were female and not elderly, and 78 were hospitalised during the acute COVID-19 phase. The main long COVID symptoms reported were fatigue, dyspnoea, and muscle weakness. Our main findings show that abnormal metabolic profiles (such as high body mass index measurement and high triglyceride, glycated haemoglobin A1c, and ferritin levels) are more prevalent in worse long COVID presentations (such as previous hospitalisation and more long-term symptoms). This prevalence may suggest a propensity for patients with long COVID to present abnormalities in the markers involved in cardiometabolic health.


Subject(s)
COVID-19 , Humans , Female , Male , Post-Acute COVID-19 Syndrome , SARS-CoV-2 , Cross-Sectional Studies , Metabolome
13.
Metab Brain Dis ; 38(5): 1573-1579, 2023 06.
Article in English | MEDLINE | ID: mdl-36897514

ABSTRACT

Maple Syrup Urine Disease (MSUD) is an autosomal recessive inborn error of metabolism (IEM), responsible for the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, in addition to their α-keto acids α-ketoisocaproic acid (KIC), α-keto-ß-methylvaleric acid (KMV), and α-ketoisovaleric acid (KIV) in the plasma and urine of patients. This process occurs due to a partial or total blockage of the dehydrogenase enzyme activity of branched-chain α-keto acids. Oxidative stress and inflammation are conditions commonly observed on IEM, and the inflammatory response may play an essential role in the pathophysiology of MSUD. We aimed to investigate the acute effect of intracerebroventricular (ICV) administration of KIC on inflammatory parameters in young Wistar rats. For this, sixteen 30-day-old male Wistar rats receive ICV microinjection with 8 µmol KIC. Sixty minutes later, the animals were euthanized, and the cerebral cortex, hippocampus, and striatum structures were collected to assess the levels of pro-inflammatory cytokines (INF-γ; TNF-α, IL-1ß). The acute ICV administration of KIC increased INF-γ levels in the cerebral cortex and reduced the levels of INF-γ and TNF-α in the hippocampus. There was no difference in IL-1ß levels. KIC was related to changes in the levels of pro-inflammatory cytokines in the brain of rats. However, the inflammatory mechanisms involved in MSUD are poorly understood. Thus, studies that aim to unravel the neuroinflammation in this pathology are essential to understand the pathophysiology of this IEM.


Subject(s)
Maple Syrup Urine Disease , Tumor Necrosis Factor-alpha , Rats , Animals , Male , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism , Oxidative Stress , Keto Acids/pharmacology , Maple Syrup Urine Disease/drug therapy , Maple Syrup Urine Disease/metabolism , Amino Acids, Branched-Chain/metabolism
14.
Biomolecules ; 13(1)2023 01 12.
Article in English | MEDLINE | ID: mdl-36671542

ABSTRACT

In a previous work, the common gonadotrophic hormone α-subunit (ag-GTHα), the ag-FSH ß- and ag-LH ß-subunit cDNAs, were isolated and characterized by our research group from A. gigas pituitaries, while a preliminary synthesis of ag-FSH was also carried out in human embryonic kidney 293 (HEK293) cells. In the present work, the cDNA sequence encoding the ag-growth hormone (ag-GH) has also been isolated from the same giant Arapaimidae Amazonian fish. The ag-GH consists of 208 amino acids with a putative 23 amino acid signal peptide and a 185 amino acid mature peptide. The highest identity, based on the amino acid sequences, was found with the Elopiformes (82.0%), followed by Anguilliformes (79.7%) and Acipenseriformes (74.5%). The identity with the corresponding human GH (hGH) amino acid sequence is remarkable (44.8%), and the two disulfide bonds present in both sequences were perfectly conserved. Three-dimensional (3D) models of ag-GH, in comparison with hGH, were generated using the threading modeling method followed by molecular dynamics. Our simulations suggest that the two proteins have similar structural properties without major conformational changes under the simulated conditions, even though they are separated from each other by a >100 Myr evolutionary period (1 Myr = 1 million years). The sequence found will be used for the biotechnological synthesis of ag-GH while the ag-GH cDNA obtained will be utilized for preliminary Gene Therapy studies.


Subject(s)
Growth Hormone , Human Growth Hormone , Animals , Humans , Growth Hormone/metabolism , DNA, Complementary/genetics , DNA, Complementary/metabolism , HEK293 Cells , Base Sequence , Cloning, Molecular , Fishes/genetics , Fishes/metabolism , Human Growth Hormone/genetics
15.
Biochemistry ; 62(1): 35-43, 2023 01 03.
Article in English | MEDLINE | ID: mdl-36535020

ABSTRACT

The gene encoding the p53 tumor suppressor protein is the most frequently mutated oncogene in cancer patients; yet, generalized strategies for rescuing the function of different p53 mutants remain elusive. This work investigates factors that may contribute to the low inherent stability of the wild-type p53 core domain (p53C) and structurally compromised Y220C mutant. Pressure-induced unfolding of p53C was compared to p63C, the p53 family member with the highest stability, the engineered superstable p53C hexamutant (p53C HM), and lower stability p53C Y220C cancer-associated mutant. The following pressure unfolding values (P50% bar) were obtained: p53C 3346, p53C Y220C 2217, p53C HM 3943, and p63C 4326. Molecular dynamics (MD) simulations revealed that p53C Y220C was most prone to water infiltration, followed by p53C, whereas the interiors of p53C HM and p63C remained comparably dry. A strong correlation (r2 = 0.92) between P50% and extent of interior hydration was observed. The pathways of individual water molecule entry and exit were mapped and analyzed, revealing a common route preserved across the p53 family involving a previously reported pocket, along with a novel surface cleft, both of which appear to be targetable by small molecules. Potential determinants of propensity to water incursion were assessed, including backbone hydrogen bond protection and combined sequence and structure similarity. Collectively, our results indicate that p53C has an intrinsic susceptibility to water leakage, which is exacerbated in a structural class mutant, suggesting that there may be a common avenue for rescuing p53 function.


Subject(s)
Neoplasms , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/metabolism , Water/metabolism , Molecular Dynamics Simulation , Neoplasms/metabolism , Biophysical Phenomena
16.
Environ Sci Pollut Res Int ; 30(10): 27030-27040, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36376647

ABSTRACT

Glyphosate-based herbicides can be harmful to the environment and human health. Especially in developing countries, these herbicides are often used indiscriminately in agricultural and urban areas. Here, we optimized a simple and efficient flow injection-based spectrophotometric method to monitor environmentally relevant glyphosate concentrations in surface waters. The method was then used to assess the environmental mobility of glyphosate in Southeast Brazil by monitoring surface runoff from experimental agricultural soil plots that received glyphosate applications in 2015. Further, water samples from low-order streams were collected in five agricultural, urban, and natural areas, as well as from the 5th-order Rio das Mortes during the rainy season. Finally, 20 drinking water sources were sampled in urban, rural, and agricultural areas. Runoff from reference plots without glyphosate application showed concentrations below the method's detection limit of 0.49 mg.L-1, whereas runoff from plots with standard glyphosate application had concentrations between 1.24 and 6.1 mg.L-1. Similarly, concentrations in natural stream water were below the detection limit, whereas agricultural streams had concentrations of up to 3.7 mg.L-1 (average: 0.97 mg.L-1). In an agricultural stream monitored weekly, concentration peaks were observed after glyphosate applications by farmers, and concentrations were correlated to stream discharge. Urban streams had concentrations of up to 5.8 mg.L-1 (average: 2.6 mg.L-1), but samples from the catchment's major river were mostly below detection limits, illustrating the dilution of urban and agricultural runoff in high-order rivers. In the sampled drinking water resources, glyphosate pollution occurred mainly in the rainy season, with detectable concentrations between 0.5 and 8.7 mg.L-1 in 80% of the sampled drinking water sources. In conclusion, our results suggest considerable environmental mobility of glyphosate in the studied Southeast Brazilian catchment. Substantial pollution, well above national and international limits, was detected in surface runoff, stream water, and drinking water resources.


Subject(s)
Drinking Water , Herbicides , Water Pollutants, Chemical , Humans , Brazil , Water Pollutants, Chemical/analysis , Environmental Monitoring , Herbicides/analysis , Glyphosate
17.
Arq. ciências saúde UNIPAR ; 27(6): 2732-2759, 2023.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1436671

ABSTRACT

O estudo objetivou identificar na literatura o nível de coordenação motora em amostra brasileira com os testes KTK e TCMB e, secundariamente quais variáveis se relacionaram com maior frequência a este construto. As bases de dados consultadas quanto ao tema, no período de 2017 a 2023, foram PubMed, Scielo, SportDiscus e a plataforma de pesquisa Google Scholar. Utilizou-se a ferramenta de checklist PRISMA e os critérios de elegibilidade do PICOs, ainda as palavras-chave foram "coordenação motora, KTK" e "Coordenação motora, TCMB" nos idiomas português, inglês e espanhol. Após triagem com critérios definidos, 26 artigos foram selecionados para compor a amostra, com um total de 4.035 crianças envolvidas nos estudos. A análise descritiva apontou que os anos 2018 (19%) e 2021 (30%) apresentaram maior quantitativo de publicações com avaliação da coordenação motora em amostra brasileira. Observou- se por meio dos resultados classificação de coordenação motora "Regular" entre os estudos que utilizaram o TCMB e classificação "Coordenação Normal" entre a maioria dos estudos que avaliaram a CM por meio do KTK. Em relação as variáveis relacionadas com a CM, identificou-se o IMC e a aptidão física as mais frequentes encontradas nos estudos. Conclui-se que o TCMB teve maior aplicabilidade para amostra de praticantes de esportes, enquanto o KTK apresentou maior número de avaliação entre escolares.


The study aimed to identify, in a Brazilian sample, the level of motor coordination in the literature with the KTK and MBCT tests and which variables were related more frequently related to this construct. The databases researched on the subject, in the period from 2017 to 2023, were PubMed, Scielo, and SportDiscus and the Google Scholar search platform. The PRISMA checklist tool and the PICOs eligibility criteria were used, and the keywords were: "motor coordination, KTK" and "motor coordination, MBCT" were used in Portuguese, English and Spanish. After screening with defined criteria, 26 articles were selected to compose the sample, with a total of 4.035 children involved in the studies. The descriptive analysis pointed out that the years 2018 (19%) and 2021 (30%) presented the highest number of publications with motor coordination assessment in the Brazilian sample. The results showed a classification of motor coordination as "Regular" among the studies that used the MBCT and a classification as "Normal Coordination" among most of the studies that assessed MC using the KTK. BMI and physical fitness were identified the most frequent found in the studies regarding the variables related to MC. It was concluded that the MBCT had greater applicability for the sample of sports practitioners, while the KTK showed a greater number of evaluations among schoolchildren.


El estudio tuvo como objetivo identificar, en una muestra brasileña, el nivel de coordinación motora en la literatura con las pruebas KTK y MBCT y qué variables se relacionaron con mayor frecuencia relacionadas con este constructo. Las bases de datos investigadas sobre el tema, en el período de 2017 a 2023, fueron PubMed, Scielo y SportDiscus y la plataforma de búsqueda Google Scholar. Se utilizó la herramienta de lista de verificación PRISMA y los criterios de elegibilidad PICOs, y las palabras clave fueron: "coordinación motora, KTK" y "coordinación motora, MBCT" se utilizaron en portugués, inglés y español. Después de la selección con criterios definidos, 26 artículos fueron seleccionados para componer la muestra, con un total de 4.035 niños involucrados en los estudios. El análisis descriptivo señaló que los años 2018 (19%) y 2021 (30%) presentaron el mayor número de publicaciones con evaluación de la coordinación motora en la muestra brasileña. Los resultados mostraron una clasificación de la coordinación motora como "Regular" entre los estudios que utilizaron el MBCT y una clasificación como "Coordinación Normal" entre la mayoría de los estudios que evaluaron la CM utilizando el KTK. El IMC y el estado físico fueron identificados como los más frecuentes en los estudios en cuanto a las variables relacionadas con la CM. Se concluyó que el MBCT tuvo mayor aplicabilidad para la muestra de practicantes deportivos, mientras que el KTK presentó mayor número de evaluaciones entre escolares.

18.
J Chem Inf Model ; 62(22): 5746-5761, 2022 11 28.
Article in English | MEDLINE | ID: mdl-36343333

ABSTRACT

The enzyme enoyl-ACP reductase (FabI) is the limiting step of the membrane's fatty acid biosynthesis in bacteria and a druggable target for novel antibacterial agents. The FabI active form is a homotetramer, which displays the highest affinity to inhibitors. Herein, molecular dynamics studies were carried out using the structure of FabI in complex with known inhibitors to investigate their effects on tetramerization. Our results suggest that multimerization is essential for the integrity of the catalytic site and that inhibitor binding enables the multimerization by stabilizing the substrate binding loop (SBL, L:195-200) coupled with changes in the H4/5 (QR interface). We also observed that AFN-1252 (naphtpyridinone derivative) promotes unique conformational changes affecting monomer-monomer interfaces. These changes are induced by AFN-1252 interaction with key residues in the binding sites (Ala95, Tyr146, and Tyr156). In addition, the analysis of water trajectories indicated that AFN-1252 complexes allow more water molecules to enter the binding site than triclosan and MUT056399 complexes. FabI-AFN-1252 simulations show accumulation of water molecules near the Tyr146/147 pocket, which can become a hotspot to the design of novel FabI inhibitors.


Subject(s)
Aquaporins , Triclosan , Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/chemistry , Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Water/metabolism , Enzyme Inhibitors/pharmacology
20.
An Acad Bras Cienc ; 94(suppl 1): e20210840, 2022.
Article in English | MEDLINE | ID: mdl-35384978

ABSTRACT

Currently, antimicrobial resistance has become a global public health problem, which has made the need for new antimicrobial compounds to deal with resistant infections an emergency. However, environments that once offered so many innovative molecules, now already exhaustively exploited, do not meet this need. In this context, a geographically isolated, under-explored and extreme environment, such as Antarctica, which holds organisms with unique physiological and biochemical characteristics, assumes great importance as a potential source of new compounds with antimicrobial activity. In this patent review, we investigate the state of technological development in the field of antimicrobial compounds obtained from Antarctic organisms, highlighting the main countries and researchers active in the field, the species utilized, the compounds obtained, and their possible therapeutic applications. As results, few patent documents were found, however they encompass a wide diversity of compounds and species, indicating a great antimicrobial potential present in Antarctic biota, including compounds active against the most important human pathogenic microorganisms, such as including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp. and multi-resistant Mycobacterium tuberculosis. Furthermore, due to the increasing trend in patent applications, a significant rise in the number of patents in this area is expected in the coming years.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Antarctic Regions , Anti-Bacterial Agents/pharmacology , Humans
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