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Yeast supplementation potentiates fluoxetine's anti-depressant effect in mice via modulation of oxido-inflammatory, CREB, and MAPK signaling pathways

IntroductionThe therapeutic potential of yeast in the management of depression is unknown. Thus, we evaluated the modulatory effect of nutritional yeast supplementation on antidepressant activity of fluoxetine in mice models of depressive-like behaviors (DLB). MethodsA total of 112 mice were divided into 16 groups (n = 7 each) for a 3-stage study. Stage I (non-DLB study) had groups Ia (10 mL/kg vehicle), Ib (20 mg/kg fluoxetine), Ic – If (2% yeast diet for all, but Id - If additionally received 5 mg/kg, 10 mg/kg, and 20 mg/kg fluoxetine respectively). Stage II (lipopolysaccharide [LPS] model of DLB) had groups IIa - IIb (10 mL/kg vehicle), IIc (20 mg/kg fluoxetine), IId (yeast) and IIe (yeast + 20 mg/kg fluoxetine). After these treatments for 24 days, animals in IIb - IIe received 0.83 mg/kg of LPS on the 25th day. Except for group IIIa (10 mL/kg vehicle), animals in other groups of stage III (unpredictable chronic mild stress [UCMS] model) were exposed to UCMS for 24 days along with 10 mL/kg vehicle (IIIb), 20 mg/kg fluoxetine (IIIc), yeast (IIId), or yeast + fluoxetine (IIIe). ResultsYeast and fluoxetine attenuated LPS- and UCMS-induced immobility, derangement of oxido-inflammatory (TNF-α, IL-6, NO, MDA, SOD, GSH, CAT, and AChE) and CREB/MAPK pathways. While fluoxetine had more potent effect than yeast when used separately, pre-treatment of mice with their combination had more pronounced effect than either of them. ConclusionYeast supplementation improves the antidepressant activity of fluoxetine in mice by modulating oxido-inflammatory, CREB, and MAPK pathways.

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Investigating the role of CFTR in human and mouse myometrium

BackgroundAbnormal cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) has been linked to airway smooth muscle abnormalities including bronchial hyperresponsiveness. However, a role for CFTR in other types of smooth muscle, including myometrium, remains largely unexplored. As CF life expectancy and the number of pregnancies increases, there is a need for an understanding of the potential role of CFTR in myometrial function. MethodsWe investigated the role of CFTR in human and mouse myometrium. We used immunofluorescence to identify CFTR expression, and carried out contractility studies on spontaneously contracting term pregnant and non-pregnant mouse myometrium and term pregnant human myometrial biopsies from caesarean sections. ResultsCFTR was found to be expressed in term pregnant mouse myometrium. Inhibition of CFTR, with the selective inhibitor CFTRinh-172, significantly reduced contractility in pregnant mouse and human myometrium in a concentration-dependent manner (44.89 ± 11.02 term pregnant mouse, 9.23 ± 4.75 term-pregnant human; maximal effect at 60 μM expressed as a percentage of the pre-treatment control period). However, there was no effect of CFTRinh-172 in non-pregnant myometrium. ConclusionThese results demonstrate decreased myometrial function when CFTR is inhibited, which may have implications on pregnancy and labour outcome and therapeutic decisions for labour in CF patients.

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Open Access
Unveiling the ethical void: Bias in reference citations and its academic ramifications

Citation bias receives scant attention in discussions of ethics. However, inaccurate citation may lead to significant distortions in scientific understanding. Although ethnical and gender citation disparities have been proposed as critical aspects, there are other contributors to citation distortions, like region-based citation bias, that, although less recognized within the scientific community, are equally important. While the foundations of scientific citation include acknowledging pioneers, giving credit to related work, and providing background reading, other more subjective or even questionable criteria are often used when constructing a reference lists. Here, we discuss the potential causes and ethical concerns of citation bias, emphasizing the role of international- or region-based citation bias as one of the most harmful aspects of this ethical breach. We argue that the international scientific community should be aware of this problem and recognize its consequences, which include hindering the accurate dissemination of science, marginalizing underrepresented voices in academia, and impeding scientific progress. We advocate that scientists should compile their reference lists with the same seriousness and integrity they apply to all other aspects of their research.

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Immediate effects of passion fruit juice supplementation on working ability and attention in healthy participants

This study investigated the effects of a single consumption of passion fruit juice (PFJ) on working ability and attention. It included 14 healthy participants aged 20–30 years. Participants randomly consumed either placebo or 50% PFJ at 3.5 mL/kg body mass. Each intervention was divided into two phases (before and after consumption). Before consumption, the participants underwent blood glucose, blood pressure, and heart rate examinations. Then, working ability and attention were evaluated. Thereafter, the blood glucose, blood pressure, and heart rate were repeatedly examined. Next, the participants completed consumption. After consumption, the participants underwent the same experiments performed before consumption. The total working ability scores after consumption were significantly high in both interventions (P < 0.05). However, PFJ intervention had a significantly higher working ability at 1, 2, 3, 4, and 5 min than placebo intervention (P < 0.05). Moreover, PFJ intervention had greater increases in attention than placebo intervention. There were no significant differences in attention between two interventions. The blood glucose levels were significantly lower in PFJ intervention than in placebo intervention both before the working ability test and after the attention test (P < 0.05). A single consumption of PFJ improved working ability in healthy participants. This may be enhanced by improving attentional focus and maintaining postprandial blood glucose.

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Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments

Human monoamine transporters (MATs) are critical to regulating monoaminergic neurotransmission by translocating their substrates from the synaptic space back into the presynaptic neurons. As such, their primary substrate binding site S1 has been targeted by a wide range of compounds for treating neuropsychiatric and neurodegenerative disorders including depression, ADHD, neuropathic pain, and anxiety disorders. We present here a comparative study of the structural dynamics and ligand-binding properties of two MATs, dopamine transporter (DAT) and serotonin transporter (SERT), with focus on the allosteric modulation of their transport function by drugs or substrates that consistently bind a secondary site S2, proposed to serve as an allosteric site. Our systematic analysis of the conformational space and dynamics of a dataset of 50 structures resolved for DAT and SERT in the presence of one or more ligands/drugs reveals the specific residues playing a consistent role in coordinating the small molecules bound to subsites S2–I and S2-II within S2, such as R476 and Y481 in dDAT and E494, P561, and F556 in hSERT. Further analysis reveals how DAT and SERT differ in their two principal modes of structural changes, PC1 and PC2. Notably, PC1 underlies the transition between outward- and inward-facing states of the transporters as well as their gating; whereas PC2 supports the rearrangements of TM helices near the S2 site. Finally, the examination of cross-correlations between structural elements lining the respective sites S1 and S2 point to the crucial role of coupled motions between TM6a and TM10. In particular, we note the involvement of hSERT residues F335 and G338, and E493-E494-T497 belonging to these two respective helices, in establishing the allosteric communication between S1 and S2. These results help understand the molecular basis of the action of drugs that bind to the S2 site of DAT or SERT. They also provide a basis for designing allosteric modulators that may provide better control of specific interactions and cellular pathways, rather than indiscriminately inhibiting the transporter by targeting its orthosteric site.

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Rib cage contributions to inspiratory capacity in patients with cervical spinal cord injury

BackgroundCervical spinal cord injury (CSI) often leads to impaired respiratory function, affecting the overall well-being of patients. This study aimed to investigate the influence of rib cage motion on inspiratory capacity in CSI patients. MethodsWe conducted a study with 11 CSI patients, utilising respiratory inductance plethysmography (RIP). We measured ventilatory volume by spirometry concurrently with RIP. Participants were instructed to perform maximal inspiratory efforts. Inspiratory capacity (IC) was calculated from spirometry waveforms. We converted the respiratory waveforms of the chest and abdomen into inspiratory volume measured by a spirometer. The inspiratory volume measured by the chest sensor was defined as VRIP-rib cage (VRIP-rc), and the inspiratory volume measured by the abdominal sensor was defined as VRIP-abdomen (VRIP-ab). Subsequently, the relationships of IC with VRIP-rc and VRIPab were assessed. ResultsThe mean IC was 1.828 ± 0.459 L, with the mean VRIP-rc at 1.343 ± 0.568 L and the mean VRIP-ab at 0.485 ± 0.427 L. A significant correlation was observed between IC and VRIP-rc (r = 0.67, p = 0.02), indicating that rib cage motion significantly influences IC in CSI patients. ConclusionThis study highlights the importance of rib cage motion in assessing inspiratory capacity in patients with CSI.

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Open Access
Cell-based homologous expression system for in-vitro characterization of environmental effects on transmembrane peptide transport in fish

All organisms encounter environmental changes that lead to physiological adjustments that could drive evolutionary adaptations. The ability to adjust performance in order to cope with environmental changes depends on the organism's physiological plasticity. These adjustments can be reflected in behavioral, physiological, and molecular changes, which interact and affect each other. Deciphering the role of molecular adjustments in physiological changes will help to understand how multiple levels of biological organization are synchronized during adaptations. Transmembrane transporters, which facilitate a cell's interaction with its surroundings, are prime targets for molecular studies of the environmental effects on an organism's physiology. Fish are subjected to environmental fluctuations and exhibit different coping mechanisms. To study the molecular adjustments of fish transporters to their external surrounding, suitable experimental systems must be established. The Mozambique tilapia (Oreochromis mossambicus) is an excellent model for environmental stress studies, due to its extreme salinity tolerance. We established a homologous cellular-based expression system and uptake assay that allowed us to study the effects of environmental conditions on transmembrane transport. We applied our expression system to investigate the effects of environmental conditions on the activity of PepT2, a transmembrane transporter critical in the absorption of dietary peptides and drugs. We created a stable, modified fish cell-line, in which we exogenously expressed the tilapia PepT2, and tested the effects of water temperature and salinity on the uptake of a fluorescent di-peptide, β-Ala-Lys-AMCA. While temperature affected only Vmax, medium salinity had a bi-directional effect, with significantly reduced Vmax in hyposaline conditions and significantly increased Km in hypersaline conditions. These assays demonstrate the importance of suitable experimental systems for fish ecophysiology studies. Furthermore, our in-vitro results show how the effect of hypersaline conditions on the transporter activity can explain expression shifts seen in the intestine of saltwater-acclimated fish, emphasizing the importance of complimentary studies in better understanding environmental physiology. This research highlights the advantages of using homologous expression systems to study environmental effects encountered by fish, in a relevant cellular context. The presented tools and methods can be adapted to study other transporters in-vitro.

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Effect of a cajuína hydroelectrolytic drink on the physical performance and hydration status of recreational runners

Cajuína is a processed drink derived from cashew and is widely consumed in the northeast region of Brazil. This study evaluated the effect of a cajuína-based hydroelectrolytic drink on the aerobic performance and hydration status of recreational runners. Seventeen males (31.9 ± 1.6 years, 51.0 ± 1.4 ml/kg/min) performed three time-to-exhaustion running sessions on a treadmill at 70% VO2max, ingesting cajuína hydroelectrolytic drink (CJ), high carbohydrate commercial hydroelectrolytic drink (CH) and mineral water (W) every 15 min during the running test. The participants ran 80.3 ± 8.4 min in CJ, 70.3 ± 6.8 min in CH and 71.8 ± 6.9 min in W, with no statistical difference between procedures. Nevertheless, an effect size of η2 = 0.10 (moderate) was observed. No statistical difference was observed in the concentrations of sodium, potassium, and osmolality in both serum and urine between the three conditions. However, the effect size was moderate (urine sodium) and high (serum sodium, potassium, and osmolality). Urine specific gravity, sweating rate and heart rate were not significantly different between drinks. The cajuína-based hydroelectrolytic drink promotes similar effects compared to commercial hydroelectrolytic drink and water, considering specific urine gravity, heart rate, sweating, and time to exhaustion in recreational runners.

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