Biology subjects

Oliveira, A. S.

Publications and source records attributed to Oliveira, A. S..

5 recordsLinked to original sources

bioRxiv2025

Isoflavone treatment attenuates cardiovascular-kidney-metabolic (CKM) syndrome symptoms in an experimental model of ovariectomized rats.

Cardiovascular-kidney-metabolic (CKM) syndrome represents an integrated spectrum of obesity, type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease, driven by shared metabolic, inflammatory, and fibrotic mechanisms. Menopause-related estrogen deficiency exacerbates these disturbances, increasing susceptibility to metabolic syndrome and renal injury. This study investigated whether dietary supplementation with soy isoflavones attenuates obesity-associated kidney injury in ovariectomized rats exposed to a high-fat, high-caloric diet. Female Wistar rats underwent bilateral ovariectomy and were assigned to control diet, hipercaloric diet (DH), or DH supplemented with isoflavones (DH+ISO). Metabolic, biochemical, oxidative stress, histopathological, and inflammatory parameters were evaluated over 120 days. The DH diet induced weight gain, hypertension, dyslipidemia, hyperglycemia, impaired renal function, increased oxidative stress, and tubulointerstitial injury, consistent with a CKM phenotype. Isoflavone supplementation did not prevent diet-induced weight gain but attenuated systolic blood pressure elevation and improved lipid and glycemic profiles. Renal function was partially preserved in DH+ISO rats, as evidenced by lower plasma creatinine levels, improved creatinine clearance, reduced urea levels, and decreased urinary peroxide excretion compared with DH animals. Histopathological analysis revealed persistent tubular injury in both DH groups, although inflammatory and oxidative markers were attenuated in isoflavone-treated rats. Immunohistochemistry demonstrated reduced renal IL-6 expression in the DH+ISO group, accompanied by trends toward decreased macrophage infiltration and IL-1{beta} expression. Collectively, these findings indicate that soy isoflavones mitigate metabolic, inflammatory, and oxidative pathways implicated in obesity-related kidney injury in a postmenopausal experimental model. Isoflavone supplementation may represent a complementary therapeutic strategy for attenuating CKM-related renal damage associated with modern diets and estrogen deficiency.

pathology↗

bioRxiv2025

On the accuracy of methods identifying gait events using optical motion capture and a single inertial measurement unit on the sacrum

Gait events (i.e., heel strikes and toe-offs) are essential for extracting spatiotemporal parameters and segmenting biological signals. While force platforms and optical motion capture (OMC) are ideal for identifying such events, inertial measurement units (IMUs) are cheaper and more applicable, especially for applications outside traditional lab settings. This study aimed to compare IMU- and OMC-based gait event detection to force plates. Seventeen adults walked on a walkway, stepping on two force plates while an IMU on the sacrum and retro-reflective markers on the calcaneus and 5th metatarsus captured foot kinematics. Gait events were identified using two OMC and two IMU methods (OMC1, OMC2, IMU1, IMU2). OMC1 detects gait events using vertical marker velocity shifts, OMC2 uses sagittal velocity thresholds, IMU1 applies wavelet-based differentiation and IMU2 identifies peaks in acceleration signals. Heel strikes and toe-offs were compared to force plate data, assessing root-mean-square error (RMSE), and intra-subject coefficient of variation (CoV). For heel strike events, OMC1 presented the lowest RMSE ([~]14.3ms), significantly differing from IMU1 (RMSE: 50.6ms; p<0,001) and IMU2 (RMSE: 61.1ms; p<0,001). For toe-offs, OMC1 presented the lowest RMSE ([~]17.3ms), differing from IMU1 (54.7ms; p<0,001) and IMU2 (74.8ms; p<0,001). IMU2 also showed the highest CoV ([~]23.9ms) differing from OMC1 ([~]7.1ms; p<0,001) and IMU1 (9.2ms; p<0,001). Lower accuracy and greater variability in IMU methods may stem from the approach used to detect gait events. Thus, OMC methods more accurately detect gait events than sacrum-mounted IMUs. While IMUs offer an alternative, researchers should be cautious of their accuracy and variability limitations.

bioengineering↗

bioRxiv2024

A dual strategy - in vitro and in silico - to evaluate human antitetanus mAbs addressing their potential protective action on TeNT endocytosis in primary rat neuronal cells

Tetanus disease is caused by the spore-forming bacteria Clostridium tetani. Its development starts with wounds or mucous layers of spore contact in water, soil, human, and animal feces. It is prevented by vaccination, but the lack of booster shots throughout life and age-decreased immune surveillance by immunosenescence enforces prophylactic treatment in case of accidents. The disease incident and lethality present a high index in underdeveloped countries. In cases of infection, administering antitetanus antibodies is preconized, usually derived from immunized horses or humans. Heterologous sera origin and the total protein content represent risks such as serum sickness and serum sickness-like reactions. Human sera can carry unknown viruses. The search for human monoclonal antibodies (mAbs) against TeNT (tetanus toxin) has increased in the last few years, although none has been approved. From a panel of previously identified human mAbs derived from B-cell sorting, we selected two nonrelated mAbs that bind to HCR/T (fragment C) of TeNT, showing disruption of its interaction with the cellular receptor ganglioside GT1b. To gain more insight into the TeNT inhibition effectiveness, we present results based on cellular assays and molecular docking tools. We describe TeNT internalization in neurons derived from the neonatal rat spinal cord. Adding the single mAbs prevented TeNT internalization higher than 50% under a specific experimental condition. The data validation was performed by quantitative analysis of immunofluorescence punctate staining of Alexa Fluor 647 conjugated to TeNT. We also confirmed the Synaptic Vesicle Glycoprotein (SV2) mediator role in TeNT endocytosis. The molecular docking assays to predict potential TeNT epitopes of the mAbs showed the binding of both antibodies to the heavy chain of TeNT, specifically to the HCR/T domain. A higher incidence was found between N1153 and W1289 when evaluating candidate residues for conformational epitope. AUTHOR SUMMARYTetanus neurotoxin, produced by the bacteria C. tetani, is one of the most potent toxins. The ubiquitous presence of bacteria and spores in soil, water, and human and animal feces makes their elimination impossible, and accidents occur in contact with wounds. People who work in agricultural or animal production are more susceptible to infection. In recent years, there has been an increase in groups developing human monoclonal antibodies for specific immunotherapy. Our group screened a panel of monoclonal antibodies in search of the best neutralizing compositions. This work reports convergent in vitro and in silico results on two antibodies that bind to the toxin domain, which interacts with neuronal cells and initiates the disease pathway. We show the hydrophobic interactions and hydrogen bonds that make contact between each antibody and the toxin, the entry of the toxin into the rat primary spinal cord cells, its interaction with synaptic vesicle II, and how the antibodies reduce the entry of the toxin into the cells, pointing to their neutralizing potential.

immunology↗

bioRxiv2021

The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour

The SARS-CoV-2 spike protein is the first contact point between the SARS-CoV-2 virus and host cells and mediates membrane fusion. Recently, a fatty acid binding site was identified in the spike (Toelzer et al. Science 2020). The presence of linoleic acid at this site modulates binding of the spike to the human ACE2 receptor, stabilizing a locked conformation of the protein. Here, dynamical-nonequilibrium molecular dynamics simulations reveal that this fatty acid site is coupled to functionally relevant regions of the spike, some of them far from the fatty acid binding pocket. Removal of a ligand from the fatty acid binding site significantly affects the dynamics of distant, functionally important regions of the spike, including the receptor-binding motif, furin cleavage site and fusion-peptide-adjacent regions. The results also show significant differences in behaviour between clinical variants of the spike: e.g. the D614G mutation shows a significantly different conformational response for some structural motifs relevant for binding and fusion. The simulations identify structural networks through which changes at the fatty acid binding site are transmitted within the protein. These communication networks significantly involve positions that are prone to mutation, indicating that observed genetic variation in the spike may alter its response to linoleate binding and associated allosteric communication.

biochemistry↗

bioRxiv2020

Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity

Changeux et al. recently suggested that the SARS-CoV-2 spike (S) protein may interact with nicotinic acetylcholine receptors (nAChRs). Such interactions may be involved in pathology and infectivity. Here, we use molecular simulations of validated atomically detailed structures of nAChRs, and of the S protein, to investigate this nicotinic hypothesis. We examine the binding of the Y674-R685 loop of the S protein to three nAChRs, namely the human 4{beta}2 and 7 subtypes and the muscle-like {beta}{gamma}d receptor from Tetronarce californica. Our results indicate that Y674-R685 has affinity for nAChRs and the region responsible for binding contains the PRRA motif, a four-residue insertion not found in other SARS-like coronaviruses. In particular, R682 has a key role in the stabilisation of the complexes as it forms interactions with loops A, B and C in the receptors binding pocket. The conformational behaviour of the bound Y674-R685 region is highly dependent on the receptor subtype, adopting extended conformations in the 4{beta}2 and 7 complexes and more compact ones when bound to the muscle-like receptor. In the 4{beta}2 and {beta}{gamma}d complexes, the interaction of Y674-R685 with the receptors forces the loop C region to adopt an open conformation similar to other known nAChR antagonists. In contrast, in the 7 complex, Y674-R685 penetrates deeply into the binding pocket where it forms interactions with the residues lining the aromatic box, namely with TrpB, TyrC1 and TyrC2. Estimates of binding energy suggest that Y674-R685 forms stable complexes with all three nAChR subtypes. Analyses of the simulations of the full-length S protein show that the Y674-R685 region is accessible for binding, and suggest a potential binding orientation of the S protein with nAChRs.

biochemistry↗