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1.
J Bodyw Mov Ther ; 39: 531-535, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38876680

ABSTRACT

Body composition is a fundamental component of physical fitness related to the performance of Sitting volleyball (SV) players. Also, establishing the best method for evaluating the body composition of these para-athletes would be highly necessary for this field. The purpose of this study was (1) to describe the body composition of male and female highly trained SV players, (2) to compare the values obtained from this population by two different methods and (3) to establish validity on one of these methods. Thirteen Brazilian SV national team players (five males and eight females) participated in this study. The air-displacement plethysmography (ADP) method as the criterion assessment and the skinfolds (SF) method were conducted for each player. Results showed that there were no significant differences between the values of all players, which ADP and SF measured for body fat percentage (BF%) and body density (BD) (p > 0.05). We found significantly different values between male and female players for BF% by SF (p = 0.04) and BD by SF (p = 0.04). A high degree of reliability was found between ADP and SF measures for BF% and BD. There were statistically significant positive correlations between BF% and BD in all values for both methods (p < 0.01). This pilot study suggests that considering the magnitude of space, expense, and other limitations related to the ADP method against the SF method, we recommend using the SF method, which is a valid, viable and reliable method for measuring body composition in elite SV players.


Subject(s)
Body Composition , Plethysmography , Skinfold Thickness , Volleyball , Humans , Male , Female , Volleyball/physiology , Pilot Projects , Body Composition/physiology , Young Adult , Plethysmography/methods , Reproducibility of Results , Adult , Sitting Position
2.
ACS Chem Biol ; 19(3): 669-686, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38486495

ABSTRACT

The understanding of protein-protein interaction mechanisms is key to the atomistic description of cell signaling pathways and for the development of new drugs. In this context, the mechanism of intrinsically disordered proteins folding upon binding has attracted attention. The VirB9 C-terminal domain (VirB9Ct) and the VirB7 N-terminal motif (VirB7Nt) associate with VirB10 to form the outer membrane core complex of the Type IV Secretion System injectisome. Despite forming a stable and rigid complex, VirB7Nt behaves as a random coil, while VirB9Ct is intrinsically dynamic in the free state. Here we combined NMR, stopped-flow fluorescence, and computer simulations using structure-based models to characterize the VirB9Ct-VirB7Nt coupled folding and binding mechanism. Qualitative data analysis suggested that VirB9Ct preferentially binds to VirB7Nt by way of a conformational selection mechanism at lower temperatures. However, at higher temperatures, energy barriers between different VirB9Ct conformations are more easily surpassed. Under these conditions the formation of non-native initial encounter complexes may provide alternative pathways toward the native complex conformation. These observations highlight the intimate relationship between folding and binding, calling attention to the fact that the two molecular partners must search for the most favored intramolecular and intermolecular interactions on a rugged and funnelled conformational energy landscape, along which multiple intermediates may lead to the final native state.


Subject(s)
Intrinsically Disordered Proteins , Computer Simulation , Fluorescence , Temperature , Protein Folding , Protein Binding
3.
Int J Biol Macromol ; 259(Pt 2): 129192, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38216013

ABSTRACT

Old Yellow Enzymes (OYEs) are flavin-dependent redox enzymes that promote the asymmetric reduction of activated alkenes. Due to the high importance of flavoenzymes in the metabolism of organisms, the interaction between OYEs from the parasites Trypanosoma cruzi and Leishmania braziliensis and three diterpene icetexanes (brussonol and two analogs), were evaluated in the present study, and differences in the binding mechanism and inhibition capacity of these molecules were examined. Although the aforementioned compounds showed poor and negligible activities against T. cruzi and L. braziliensis cells, respectively, the experiments with the purified enzymes indicated that the interaction occurs by divergent mechanisms. Overall, the ligands' inhibitory effect depends on their accessibility to the N5 position of the flavin's isoalloxazine ring. The results also indicated that the OYEs found in both parasites share structural similarities and showed affinities for the diterpene icetexanes in the same range. Nevertheless, the interaction between OYEs and ligands is directed by enthalpy and/or entropy in distinct ways. In conclusion, the binding site of both OYEs exhibits remarkable plasticity, and a large range of different molecules, including that can be substrates and inhibitors, can bind this site. This plasticity should be considered in drug design using OYE as a target.


Subject(s)
Chagas Disease , Leishmania braziliensis , Trypanosoma cruzi , Humans , NADPH Dehydrogenase/chemistry , NADPH Dehydrogenase/pharmacology , Chagas Disease/parasitology , Flavins/pharmacology
4.
Chem Biol Interact ; 387: 110796, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37951333

ABSTRACT

Angiogenesis is considered one of the hallmarks of cancer, assisting tumor progression and metastasis. The mesoionic compound, MI-D, can induce cell death and provoke cytoskeletal and metabolic changes in cancer cells. Using in vitro and in vivo models, this study aimed to evaluate the effects of MI-D on the viability of human endothelial cells (EC) and its ability to inhibit tumor-induced angiogenesis induced by tumoral cells. For in vitro analysis, colon carcinoma (HT29) and endothelial (EA.hy926) cells were used as the tumoral and angiogenesis models, respectively. To evaluate cytotoxicity, methylene blue viability stain and annexin-V/7AAD tests were performed with both cell types. For the angiogenesis experiments, scratch wound healing and capillary tube-like formation assays were performed with the EC. The in vivo tests were performed with the chorioallantoic membrane (HET-CAM) methodology, wherein gelatin sponge implants containing MI-D (5, 25, and 50 µM), HT29 cells, or both were grafted in the CAM. Our data showed that MI-D induced apoptosis in both endothelial and colon carcinoma cells, with a strong cytotoxic effect on the tumoral lineage. The drug inhibited the EC's migration and capillary-like structure formation in vitro. In the HET-CAM assays, MI-D reduced the number of blood vessels in the membrane when grafted alone and accompanied by tumor cells. In this study, MI-D interfered in important steps of angiogenesis, such as maintenance of endothelial cell viability, migration, formation of capillary-like structures, as well tumor-induced neovascularization, reinforcing the hypothesis that MI-D might act as an inhibitor of angiogenesis, and a potential antitumor agent.


Subject(s)
Antineoplastic Agents , Carcinoma , Humans , Endothelial Cells , Angiogenesis , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Cell Movement , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism , Antineoplastic Agents/therapeutic use , Carcinoma/metabolism , Human Umbilical Vein Endothelial Cells , Cell Proliferation
5.
Article in English | MEDLINE | ID: mdl-37957896

ABSTRACT

BACKGROUND: Chagas disease kills around 10,000 people yearly, primarily in Latin America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe, and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic compounds as bioisosteres are well known, and they are prospective candidates in the hunt for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease cruzain from T. cruzi is a validated target for disease treatment. OBJECTIVE: Thus, using a molecular dynamics simulation, the current study attempted to determine if a significant interaction occurred between the enzyme cruzain and its ligand. RESULTS: Interactions with the catalytic site and other critical locations were observed. Also, the RMSD values suggested that the molecule under research had stable interactions with its target. CONCLUSION: Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic activity of cruzain, indicating that it might be a promising antichagasic drug.

6.
Trop Anim Health Prod ; 55(6): 414, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37996715

ABSTRACT

We conducted two experiments. The first aimed to obtain and characterize microparticles of slow-release urea (SRU) using calcium alginate as the encapsulating agent. The second experiment evaluated their inclusion in sheep diets. In the first experiment, four treatments from a completely randomized design were employed to develop an SRU through the ionic gelification technique testing two drying methods (oven and lyophilizer) and addition or no of sulfur (S): SRU oven-dried with sulfur (MUSO) and without sulfur (MUO), SRU freeze-dried/lyophilized with (MUSL), and without sulfur (MUL). MUO exhibited better yield and encapsulation efficiency among these formulations than the others. Therefore, the second experiment was conducted to compare free urea (U) as control and three proportions (1%, 1.5%, and 2% of total dry matter) of MUO in the diet of sheep. Twenty-four non-castrated male Santa Ines lambs, with an average body weight of 22 ± 3.0 kg, were used and distributed in a completely randomized design with four treatments and six replications. The inclusion of 1% alginate-encapsulated urea (MUO1%) resulted in higher dry matter (DM) intake than free urea (p ≤ 0.05). MUO2% inclusion promoted higher NDF digestibility than U and MUO1%. MUO1% showed higher DM than MUO2% and higher NFC digestibility than U and MUO2% (p ≤ 0.05). Sheep fed MUO1.5% and MUO2% exhibited similar nutrient intake and digestibility. Sheep receiving MUO1% had higher N-intake, N-urinary, N-excretion total, N-digested, and N-retained compared to U. Sheep fed MUO1% showed greater N-retained (as % ingested and digested), microbial protein production, and efficiency when compared to other treatments (p ≤ 0.05). MUO2% addition (SRU) promoted the lowest microbial protein production and efficiency in sheep. MUO dietary inclusion increased feeding time and reduced idleness time compared to U, regardless of the MUO level (p ≤ 0.05). Adding MUO1% improved the intake efficiency of DM and NDF and resulted in more feed boli than the other MUO levels (p ≤ 0.05). Sheep receiving U had (4 h after fending) higher NH3-N, pH, and blood urea nitrogen (BUN) and lower TGL serum compared to sheep fed MUO (p ≤ 0.05), without significant difference among MUO levels (p > 0.05), except NH3-N was higher in MUO1.5% and MUO2% compared to MUO1.0%. The external ionic gelation technique proved suitable for urea microencapsulation in calcium alginate (3%), demonstrating high quality, efficiency, and yield. MUO represents a promising slow-release urea for ruminants and is recommended for sheep diets at an inclusion level of 1.0%. This inclusion level improves intake efficiency and nutrient digestibility, increases rumen nitrogen retention, and reduces BUN without compromising sheep health.


Subject(s)
Digestion , Urea , Animals , Male , Alginates/metabolism , Alginates/pharmacology , Animal Feed/analysis , Diet/veterinary , Nitrogen/metabolism , Rumen/metabolism , Sheep , Sulfur , Urea/metabolism
7.
Pharmaceutics ; 15(10)2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37896254

ABSTRACT

Arthropod-borne viruses within the Flaviviridae family such as Zika (ZIKV) and dengue (DENV) are responsible for major outbreaks in tropical countries, and there are no specific treatments against them. Naringenin and 7-O-methyl naringenin are flavonoids that can be extracted from geopropolis, a natural material that the Brazilian Jandaira stingless bee (Melipona subnitida Ducke) produces to protect its nest. Here, these flavonoids were tested against ZIKV and DENV using Vero cells as a cellular model to perform a cytotoxicity assay and to define the effective concentrations of TCID50 as the readout method. The results demonstrated the antiviral activity of the compounds against both viruses upon the treatment of infected cells. The tested flavonoids had antiviral activity comparable with 6-methylmercaptopurine riboside (6-MMPr), used here as a positive control. In addition, to identify the possible action mechanism of the antiviral candidates, we carried out a docking analysis followed by a molecular dynamics simulation to elucidate naringenin and 7-O-methyl naringenin binding sites to each virus. Altogether, these results demonstrate that both flavonoids have potent antiviral effects against both viruses and warrant further in vivo trials.

8.
Biomedicines ; 11(9)2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37760978

ABSTRACT

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman's capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

9.
Animals (Basel) ; 13(15)2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37570305

ABSTRACT

This study aims to evaluate the effects of increasing tannin levels from Mimosa tenuiflora hay on the intake, digestibility, and balance of nitrogen (N), water, and energy in hair lambs. Thirty-two Santa Ines lambs, at an average age of 150 days and body weight of 26.75 ± 2.29 kg, were randomly assigned to four treatments in a completely randomized design. The treatments consisted of four diets: a control diet, tannin-free, and three diets with increasing levels of total tannin, 26.2, 52.4, and 78.6 g tannin/kg dry matter (DM). Including the total tannins in the lambs' diet led to a quadratic increase in the intake of nutrients, N-retention (g/day), water intake, water absorption and retention, energy intake, and energy excretion in feces and gases. However, the digestibility of crude protein, neutral and acid detergent fibers, and total carbohydrates decreased. It was observed that there is a correlation between the variable nutrient digestibility and N-ingested and the N-absorbed, N-urinary, and N-retained. However, the N-excreted in feces did not correlate with any of the variables studied. It is recommended to include 33 g/kg DM of total natural tannins from Mimosa tenuiflora hay in the diet of hair lambs, as it improves intake, energy balance, dietary N, and body water composition while reducing the excretion of N-urinary and gas emissions to the environment.

10.
Eur J Med Chem ; 255: 115400, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37130472

ABSTRACT

Malaria can be caused by several Plasmodium species and the development of an effective vaccine is challenging. Currently, the most effective tool to control the disease is the administration of specific chemotherapy; however, resistance to the frontline antimalarials is one of the major problems in malaria control and thus the development of new drugs becomes urgent. The study presented here sought to evaluate the antimalarial activities of compounds derived from 2-amino-1,4-naphthoquinones containing 1,2,3-triazole using in vivo and in vitro models. 1H-1,2,3-Triazole 2-amino-1,4-naphthoquinone derivatives were synthesized and evaluated for antimalarial activity in vitro, using P. falciparum W2 chloroquine (CQ) resistant strain and in vivo using the murine-P. berghei ANKA strain. Acute toxicity was determined as established by the OECD (2001). Cytotoxicity was evaluated against HepG2 and Vero mammalian cell lines. Transmission electron microscopy of the Plasmodium falciparum trophozoite (early and late stages) was used to evaluate the action of compounds derived at ultra-structural level. The compounds displayed low cytotoxicity CC50 > 100 µM, neither did they cause hemolysis at the tested doses and nor the signs of toxicity in the in vivo acute toxicity test. Among the five compounds tested, one showed IC50 values in submicromolar range of 0.8 µM. Compounds 7, 8 and 11 showed IC50 values < 5 µM, and selectivity index (SI) ranging from 6.8 to 343 for HepG2, and from 13.7 to 494.8 for Vero cells. Compounds 8 and 11 were partially active against P. berghei induced parasitemia in vivo. Analysis of the ultrastructural changes associated with the treatment of these two compounds, showed trophozoites with completely degraded cytoplasm, loss of membrane integrity, organelles in the decomposition stage and possible food vacuole deterioration. Our results indicated that compounds 8 and 11 may be considered hit molecules for antimalarial drug discovery platform and deserve further optimization studies.


Subject(s)
Antimalarials , Malaria, Falciparum , Malaria , Naphthoquinones , Chlorocebus aethiops , Humans , Animals , Mice , Antimalarials/pharmacology , Antimalarials/chemistry , Naphthoquinones/chemistry , Vero Cells , Triazoles/pharmacology , Triazoles/therapeutic use , Malaria/drug therapy , Malaria, Falciparum/drug therapy , Plasmodium falciparum , Plasmodium berghei , Mammals
11.
Magn Reson Imaging ; 102: 49-54, 2023 10.
Article in English | MEDLINE | ID: mdl-37137344

ABSTRACT

PURPOSE: To develop an ABP-MRI to evaluate response to NAC for invasive breast carcinoma. STUDY TYPE: A single-center, cross-sectional study. SUBJECTS: A consecutive series of 210 women with invasive breast carcinoma who underwent breast MRI after NAC between 2016 and 2020. FIELD STRENGTH/SEQUENCE: 1.5 T / Dynamic contrast-enhanced. ASSESSMENT: MRI scans were independently reevaluated, with access to dynamic contrast-enhanced without contrast and to the first, second, and third post-contrast time (ABP-MRI 1-3). STATISTICAL TESTS: The diagnostic performance of the ABP-MRIs and the Full protocol (FP-MRI) were analyzed. The Wilcoxon non-parametric test (p-value <0.050) was used to compare the capability in measuring the most extensive residual lesion. RESULTS: The median age was 47 (24-80) years. ABP-MRI 1 showed higher specificity (84.6%; 77/91) but a higher probability of false-negatives (16.8%) and lower sensitivity (83.2%; 99/119) than ABP-MRI 2,3 and the FP-MRI, which were identical in specificity (81.3%; 74/91), probability of false-negatives (8.4%), and sensitivity (91.6%; 109/119). ABP-MRI 2 showed a mean underestimation of only 0.03 cm in the measurement of the longest axis of the residual lesion (p = 0.008) with an average reduction in the acquisition time of 75%, compared with the FP-MRI. CONCLUSION: ABP-MRI 2 showed diagnostic performance equivalent to the FP-MRI with a 75% reduction in the acquisition time.


Subject(s)
Breast Neoplasms , Female , Humans , Middle Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Neoadjuvant Therapy , Cross-Sectional Studies , Breast/diagnostic imaging , Breast/pathology , Magnetic Resonance Imaging/methods , Contrast Media
12.
Trop Anim Health Prod ; 55(3): 142, 2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37016138

ABSTRACT

Rumen-protected fat (RPF) was produced in the 1st experimental stage through melt-emulsification technique using buriti oil (BO) as core, at concentrations of 10% (BO10), 20% (BO20), and 30% (BO30) (w/w), and carnauba wax (CW) as encapsulant material. After obtention and characterization, protected fat microspheres were tested in a 2nd experimental stage on the sheep' diet using six castrated 2-year-old male Santa Ines with initial weight 48.9 ± 5.23 kg, fistulated in rumen and distributed in a double Latin square design with 3 treatments × 3 periods, to evaluate rumen pH, temperature, protozoal count, and blood parameters. There was no difference (P > 0.05) among RPF microspheres for microencapsulation yield. However, microencapsulation efficiency increased (P < 0.05) with BO addition ranging from 36 to 61.3% for BO10 and BO30, respectively. The inclusion of BO10 in the sheep's diet did not affect the ruminal dry matter degradability (DMD) of BO over time (P > 0.05); however, BO20 and BO30 had higher (P < 0.05) DMD values than BO10. No significant differences were observed among RPF for rumen pH and temperature (P > 0.05). There was an increase (P < 0.05) in the protozoal population in the rumen environment due to the microencapsulated BO30 inclusion. There was also increase (P < 0.05) in serum albumin, cholesterol, aspartate aminotransferase (ALT), and gamma-glutamyltransferase (GGT), and a reduction (P < 0.05) in serum triglycerides of the sheep when RPF microspheres increased in the diet. Melt-emulsification proved to be a good technique for microencapsulation of buriti oil into the carnauba wax matrix. RPF from buriti oil protected into carnauba wax is recommended for sheep diet because it increases energy density, without adverse effects on the protozoal populations and blood serum metabolites from the bypass effect in the rumen.


Subject(s)
Diet , Rumen , Animals , Male , Animal Feed/analysis , Diet/veterinary , Dietary Supplements , Digestion , Fermentation , Rumen/metabolism , Sheep
13.
Front Vet Sci ; 10: 1032429, 2023.
Article in English | MEDLINE | ID: mdl-36937008

ABSTRACT

A better understanding of the nutritional requirements of sheep, especially in terms of minerals, is crucial for improving production. We estimated the net requirements for Ca, P, K, Mg, and Na for gain (NCag, NPg, NKg, NMgg, and NNag) and maintenance (NCam, NPm, NKm, NMgm, and NNam) in male and female hair sheep. Six datasets with 248 individual records of hair sheep (139 non-castrated males, 75 castrated males and 34 females) were used to estimate the net macromineral requirements for gain. To estimate the net macromineral requirements for maintenance, 52 observations (26 non-castrated and 26 castrated males) were used. A meta-analytical approach was applied, using non-linear mixed effects models and the study as a random effect. Based on information criteria for model selection, heterogeneous variance functions were more likely to describe mineral requirements with a low level of model selection uncertainty. The adopted criteria allowed the choice of the best models to represent the macromineral requirements. The chosen models explained the observed variability in the sex, and the choices were based on a low level of uncertainty (w ≥ 0.90). Irrespective of sex, NCag and NPg decreased with increasing BW from 10 to 30 kg and average daily gain (ADG) of 150 g/day, ranging from 1.71-1.38; 1.83-1.57; 1.82-1.51 of Ca and 0.86-0.66; 0.92-0.78; 0.92-0.75 of P for non-castrated males, castrated males, and females, respectively. The NKg remained constant, with mean values of 0.26 g/day. The NNag range was 0.17 to 0.14 g/day for non-castrated males, 0.20 to 0.25 g/day for females, and constant (0.18 g/day) for castrated males with an increase in BW from 10 to 30 kg and an ADG of 150 g/day. Macromineral requirements for maintenance (mg/kg BW) and retention (%) were 23.70 and 54.30 for Ca, 25.33 and 79.80 for P, 11.74 and 5.00 for K, 2.63 and 8.50 for Mg, and 7.01 and 8.10 for Na for males. The International Committees did not provide inferences about the sex influence on mineral requirements. Our study indicates that sex is one factor that influences the macromineral requirements for gain. The information generated in this study can be used to optimize the mineral management of hair sheep in the growing phase in tropical regions.

14.
Nucleic Acids Res ; 51(2): 919-934, 2023 01 25.
Article in English | MEDLINE | ID: mdl-36583339

ABSTRACT

Protein synthesis by the ribosome requires large-scale rearrangements of the 'small' subunit (SSU; ∼1 MDa), including inter- and intra-subunit rotational motions. However, with nearly 2000 structures of ribosomes and ribosomal subunits now publicly available, it is exceedingly difficult to design experiments based on analysis of all known rotation states. To overcome this, we developed an approach where the orientation of each SSU head and body is described in terms of three angular coordinates (rotation, tilt and tilt direction) and a single translation. By considering the entire RCSB PDB database, we describe 1208 fully-assembled ribosome complexes and 334 isolated small subunits, which span >50 species. This reveals aspects of subunit rearrangements that are universal, and others that are organism/domain-specific. For example, we show that tilt-like rearrangements of the SSU body (i.e. 'rolling') are pervasive in both prokaryotic and eukaryotic (cytosolic and mitochondrial) ribosomes. As another example, domain orientations associated with frameshifting in bacteria are similar to those found in eukaryotic ribosomes. Together, this study establishes a common foundation with which structural, simulation, single-molecule and biochemical efforts can more precisely interrogate the dynamics of this prototypical molecular machine.


Subject(s)
Ribosome Subunits , Ribosomes , Eukaryota/cytology , Protein Biosynthesis , Ribosome Subunits/genetics , Ribosomes/metabolism , Rotation , Prokaryotic Cells , Biomechanical Phenomena
15.
J Phys Chem B ; 126(51): 10854-10869, 2022 12 29.
Article in English | MEDLINE | ID: mdl-36519977

ABSTRACT

The computer-designed Top7 served as a scaffold to produce immunoreactive proteins by grafting of the 2F5 HIV-1 antibody epitope (Top7-2F5) followed by biotinylation (Top7-2F5-biotin). The resulting nonimmunoglobulin affinity proteins were effective in inducing and detecting the HIV-1 antibody. However, the grafted Top7-2F5 design led to protein aggregation, as opposed to the soluble biotinylated Top7-2F5-biotin. The structure-based model predicted that the thermodynamic cooperativity of Top7 increases after grafting and biotin-labeling, reducing their intermediate state populations. In this work, the folding kinetic traps that might contribute to the aggregation propensity are investigated by the diffusion theory. Since the engineered proteins have similar sequence and structural homology, they served as protein models to study the kinetic intermediate traps that were uncovered by characterizing the position-dependent drift-velocity (v(Q)) and the diffusion (D(Q)) coefficients. These coordinate-dependent coefficients were taken into account to obtain the folding and transition path times over the free energy transition states containing the intermediate kinetic traps. This analysis may be useful to predict the aggregated kinetic traps of scaffold-epitope proteins that might compose novel diagnostic and therapeutic platforms.


Subject(s)
Biotin , Protein Folding , Biotin/metabolism , Proteins/chemistry , Thermodynamics , Epitopes , HIV Envelope Protein gp41 , HIV Antibodies
16.
Foods ; 11(23)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36496572

ABSTRACT

This study aims to evaluate the quality of salted sun-dried meat from young bulls (Nellore cattle) fed with a diet containing 0.0, 0.5, 1.0 and 1.5% of lauric acid in the total dry matter (DM). Thirty-two Nellore bulls with initial body weight of 368 ± 32 kg were used. A linear decrease (p < 0.05) in pH and protein content of the salted sun-dried meat was observed with the inclusion of lauric acid. The moisture, ash, lipid, collagen content, water-holding capacity, cooking loss, color indexes (L*, a*, b*, C*), and shear force were not affected. Lipid oxidation at 7 days of storage increased linearly in the salted sun-dried meat. Most of the fatty acid composition of the salted sun-dried meat from the semimembranosus muscle of young bulls was not influenced (p > 0.05) by the lauric acid inclusion in the bulls' diet. However, there was a linear increase (p < 0.05) in the SFA lauric acid (C12:0), PUFAn-3 EPA (C20:5n − 3) and DHA (C22:6n − 3), and a quadratic increase in the PUFAn-6 arachidonic (C20:4n − 6) due to lauric acid addition from palm kernel oil in the diet. There was a liner increase (p < 0.05) in the total ∑PUFA, ∑n − 6, ∑n − 3 contents of salted sun-dried meat from the semimembranosus muscle of young bulls and the h:H health index of the level of lauric acid inclusion in bull's diet. In contrast, the thrombogenicity health index (TI) and ∑n − 6:∑n − 3 ratio content in salted sun-dried meat from the semimembranosus muscle of young bulls presented a linear decrease (p < 0.05) due to lauric acid addition in the bulls' diet. Lauric acid (C12:0) inclusion up to 1.5% in the diet of young Nellore bull improved the fatty acid composition of the salted sun-dried meat, increasing EPA, DHA, n − 6 and n − 3, TI, and h:H indexes, which are associated with a better lipid quality of meat products, and further improves tenderness at the highest concentration.

17.
Animals (Basel) ; 12(23)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36496763

ABSTRACT

This study evaluated the effects of palm kernel oil (PKO) in the diet of lambs on carcass characteristics, quality, and fatty acid profile of the meat. Forty uncastrated male Santa Inês lambs were used and divided among the treatments: PKOzero without inclusion; PKO1.3­added 1.3%; PKO2.6­added 2.6%; PKO3.9­added 3.9%; PKO5.2­added 5.2%. The carcass characteristics, the variables related to meat color, and the chemical composition of the Longissimus lumborum of lambs were not affected by the PKO inclusion. The weight of the carcasses at slaughter, hot and cold, half carcass, loin-eye area, and commercial cuts decreased linearly when PKO was added to the lamb diet (p < 0.01). CCY decreased linearly to the inclusion level of 2.66% PKO (RMSE 2.204). Total conjugated linoleic acid CLA and C18:3 n-3 GA concentrations remained stable until the inclusion levels of 3.44% PKO (RMSE 0.0956) and 2.17% (RMSE 0.0637), decreasing its concentrations as the increased level of PKO. The presence of PKO in the lambs' diet up to the level of 5.2% did not change the meat quality characteristics; thus, from the point of view of lamb meat production and fatty acid profile, the inclusion of PKO is not beneficial.

18.
Animals (Basel) ; 12(23)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36496764

ABSTRACT

We aimed to determine the optimal inclusion level of sunflower cake (0, 90, 180, and 270 g/kg total DM) as a partial replacement of soybean meal and corn ground in young bulls' diets by examining nutrient intake and digestibility, ingestive behavior, nitrogen balance, metabolic serum profile, growth performance, and carcass traits. Thirty-two intact Nellore bulls (BW 374 ± 42.5) were distributed in a completely randomized design. The experiment lasted 90 days. The final BW of the animals was 515.25 ± 24.7. There was a linear decrease effect in the intake of DM, crude protein and nonfibrous carbohydrates, eating and rumination efficiency, N-urinary, N-total excretion, and blood urea nitrogen. Sunflower cake did not affect the NDF digestibility, nitrogen (N)-fecal excretion, blood metabolites, Longissimus lumborum muscle area, or subcutaneous fat deposition. There were linear and quadratic effects on the eating and rumination time, microbial protein production and efficiency, gamma-glutamyl transferase and cholesterol serum concentrations, and muscle carcass tissue. There was a quadratic effect on ether extract intake, final BW, and total gain with the inclusion of sunflower cake in the young bull's diet. The replacement of soybean meal and corn ground with sunflower cake at the level of 90 g/kg of DM in the diet of young bulls is recommended because it reduces the DM intake and digestibility, increases microbial protein synthesis and muscle tissue deposition, and consequently improves the performance, feed efficiency, and carcass traits.

19.
J Inorg Biochem ; 237: 111993, 2022 12.
Article in English | MEDLINE | ID: mdl-36108344

ABSTRACT

This work describes the synthesis, characterization and in vitro anticancer activity of two platinum(II) complexes of the type [Pt(L1)2(1,10-phen)] 1 and [Pt(L2)2(1,10-phen)] 2, where L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and 1,10-phen = 1,10-phenanthroline. As to the structure of these complexes, the X-ray structural analysis of 1 indicates that the geometry around the platinum(II) ion is distorted square-planar, where two 5-alkyl-1,3,4-oxadiazol-2-thione derivatives coordinate a platinum(II) ion through the sulfur atom. A chelating bidentate phenanthroline molecule completes the coordination sphere. We tested these complexes in two breast cancer cell lines, namely, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both cells, the most lipophilic platinum compound, complex 2, was more active than cisplatin, one of the most widely used anticancer drugs nowadays. DNA binding studies indicated that such complexes are able to bind to ct-DNA with Kb values of 104 M-1. According to data from dichroism circular and fluorescence spectroscopy, these complexes appear to bind to the DNA in a non-intercalative, probably via minor groove. Molecular docking followed by semiempirical simulations indicated that these complexes showed favorable interactions with the minor groove of the double helix of ct-DNA in an A-T rich region. Thereafter, flow cytometry analysis showed that complex 2 induced apoptosis and necrosis in MCF-7 cells.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Humans , Phenanthrolines/pharmacology , Phenanthrolines/chemistry , Platinum/chemistry , Thiones , Molecular Docking Simulation , Antineoplastic Agents/chemistry , DNA/chemistry , Coordination Complexes/chemistry , Cell Line, Tumor
20.
Chem Biodivers ; 19(10): e202200119, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36094678

ABSTRACT

Alterations in lipid and lipoprotein metabolism are factors that trigger several negative metabolic complications. Hyperlipidemia is the starting point for the development of comorbidities of the cardiovascular system, such as atherosclerosis. The search for compounds that reduce high levels of total cholesterol and triglycerides has been widely reported in several publications in the literature. Phthalimide derivatives have been extensively researched with various biological actions. In this study we evaluated the antihyperlipidemic ability of three phthalimide derivatives (FGT-2, FGT-3 and FGT-4) on a model of obesity and insulin resistance in mice. The animals were submitted to a hyperlipid diet for 60 days. On the thirtieth day they were treated with phthalimides (20 mg/kg). The positive control group was treated with Simvastatin (20 mg/kg) and the negative control received only the carboxymethylcellulose vehicle. Biochemical and histological analyzes of all groups were analyzed. The animals treated with phthalimidic derivatives had a reduction in total cholesterol, low density and very low density lipoproteins (LDL-c and VLDL-c), triglycerides and fasting glycemia when compared to the negative control group. The treated animals also showed good results when analyzing the atherogenic indexes Castelli i and II and the ratio Triglycerides/HDL-c. In the oral glucose tolerance test and in the insulin tolerance test, animals treated with phthalimides were more sensitive to the action of the hormone regulating carbohydrate uptake. In the evaluation of the transaminases (AST/ALT), the animals of the group treated with phthalimides presented a lower elevation than the other groups of the experiment, the same observed with the uric acid evaluation. Histological analyzes were performed on liver, kidney, heart and pancreas samples. The groups treated with the compounds FGT-2 and FGT3 presented discrete alterations in the liver and kidney. FGT-4 did not present histological alterations for both tissues and the three phthalimide derivatives did not cause alterations in the other organs. These results suggest that the phthalimides tested can act as antihyperlipidemic agents and have a pleiotropic action, by acting also reducing glycemia in insulin resistance model mimicking diabetes mellitus type 2. These compounds may appear as a new approach in the treatment of obesity and complications, which are multifaceted.


Subject(s)
Diabetes Mellitus, Type 2 , Dyslipidemias , Insulin Resistance , Insulins , Mice , Animals , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Cholesterol, LDL , Uric Acid , Carboxymethylcellulose Sodium , Triglycerides , Dyslipidemias/drug therapy , Phthalimides/pharmacology , Lipoproteins, VLDL , Obesity/drug therapy , Simvastatin , Hormones , Transaminases
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