Characterization of metabolites and microbiota composition from human stool provides powerful insight into the molecular phenotypic difference between subjects with normal weight and those with ...overweight/obesity. The aim of this study was to identify potential metabolic and bacterial signatures from stool that distinguish the overweight/obesity state in children/adolescents. Using 1H NMR spectral analysis and 16S rRNA gene profiling, the fecal metabolic profile and bacterial composition from 52 children aged 7 to 16 was evaluated. The children were classified into three groups (16 with normal-weight, 17 with overweight, 19 with obesity). The metabolomic analysis identified four metabolites that were significantly different (p < 0.05) among the study groups based on one-way ANOVA testing: arabinose, butyrate, galactose, and trimethylamine. Significantly different (p < 0.01) genus-level taxa based on edgeR differential abundance tests were genus Escherichia and Tyzzerella subgroup 3. No significant difference in alpha-diversity was detected among the three study groups, and no significant correlations were found between the significant taxa and metabolites. The findings support the hypothesis of increased energy harvest in obesity by human gut bacteria through the growing observation of increased fecal butyrate in children with overweight/obesity, as well as an increase of certain monosaccharides in the stool. Also supported is the increase of trimethylamine as an indicator of an unhealthy state.
-resveratrol, a well-known plant phenolic compound, has been intensively investigated due to its association with the so-called French paradox. However, despite its high pharmacological potential,
...-resveratrol has shown relatively low bioavailability.
-resveratrol is intensively metabolized in the intestine and liver, yielding metabolites that may be responsible for its high bioactivity. The aim of this study was to investigate and compare the metabolism of
-resveratrol (tRes),
-resveratrol (cRes) and dihydroresveratrol (dhRes) in an in vitro epithelial model using Caco-2 cell lines. Obtained metabolites of tRes, cRes and dhRes were analyzed by LC/MS Q-TOF, and significant differences in the metabolism of each compound were observed. The majority of tRes was transported unchanged through the Caco-2 cells, while cRes was mostly metabolized. The main metabolite of both
and
resveratrol observed as a result of colon microbial metabolism, dhRes, was metabolized almost completely, with only traces of the unchanged molecule being found. A sulphate conjugate was identified as the main metabolite of tRes in our model, while a glucuronide conjugate was the major metabolite of cRes and dhRes. Since metabolism of simple phenolics and polyphenols plays a crucial role in their bioavailability, detailed knowledge of their transformation is of high scientific value.
Dietary phenolics or polyphenols are mostly metabolized by the human gut microbiota. These metabolites appear to confer the beneficial health effects attributed to phenolics. Microbial composition ...affects the type of metabolites produced. Reciprocally, phenolics modulate microbial composition. Understanding this relationship could be used to positively impact health by phenolic supplementation and thus create favorable colonic conditions. This study explored the effect of six stilbenoids (batatasin III, oxyresveratrol, piceatannol, pinostilbene, resveratrol, thunalbene) on the gut microbiota composition. Stilbenoids were anaerobically fermented with fecal bacteria from four donors, samples were collected at 0 and 24 h, and effects on the microbiota were assessed by 16S rRNA gene sequencing. Statistical tests identified affected microbes at three taxonomic levels. Observed microbial composition modulation by stilbenoids included a decrease in the Firmicutes to Bacteroidetes ratio, a decrease in the relative abundance of strains from the genus
, and effects on the family
. A frequently observed effect was a further decrease of the relative abundance when compared to the control. An opposite effect to the control was observed for
, whose relative abundance increased. Observed effects were more frequently attributed to resveratrol and piceatannol, followed by thunalbene and batatasin III.
•Whole-gene characterization (11 ORFs) for 72 randomly selected, Species A Rotaviruses of common and unusual genotypes collected in Benin from the 2016 to 2018 seasons.•All study strains exhibited ...two genetic constellations designed as Wa-like, G1/G9/G12-P6/P8-I1-R1-C1-M1-A1-N1-T1-E1-H1 and DS-1-like, G2/G3/G12-P4/P6-I2-R2-C2-M2-A2-N2-T2-E2-H2.•Genetic analysis showed identification of 2-13 and 1-17 sub-genotypic alleles for DS-1-like and Wa-like strains, respectively.
Species A rotaviruses (RVA) still play a major role in causing acute diarrhea in children under five years old worldwide. Currently, an 11-gene classification system is used to designate the full genotypic constellations of circulating strains. Viral proteins and non-structural proteins in the order VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 are represented by the genotypes Gx-Px-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx, respectively. In Benin, ROTAVAC® vaccine was introduced into the Expanded Programme on Immunization in December 2019. To monitor circulating RVA strains for changes that may affect vaccine performance, in-depth analysis of strains prior to vaccine introduction are needed. Here we report, the whole-gene characterization (11 ORFs) for 72 randomly selected RVA strains of common and unusual genotypes collected in Benin from the 2016 to 2018 seasons. The sequenced strains were 15 G1P8, 20 G2P4, 5 G9P8, 14 G12P8, 9 G3P6, 2 G1P6, 3 G2P6, 2 G9P4, 1 G12P6, and 1 G1G9P8/P4. The study strains exhibited two genetic constellations designed as Wa-like G1/G9/G12-P6/P8-I1-R1-C1-M1-A1-N1-T1-E1-H1 and DS-1-like G2/G3/G12-P4/P6-I2-R2-C2-M2-A2-N2-T2-E2-H2. Genotype G9P4 strains possessed a DS-1-like genetic constellation with an E6 NSP4 gene, G9-P4-I2-R2-C2-M2-A2-N2-T2-E6-H2. The mixed genotype showed both Wa-like and DS-1-like profiles with a T6 NSP3 gene G1/G9P8/4-I1/I2-R1/R2-C1/C2-M1/M2-A1/A2-N1/N2-T1/T6-E1/E6-H1/H2. At the allelic level, the analysis of the Benin strains, reference strains (with known alleles), vaccine strains (with known alleles) identified 2–13 and 1–17 alleles for DS-1-like and Wa-like strains, respectively. Most of the study strains clustered into previously defined alleles, but we defined 3 new alleles for the VP7 (G3 = 1 new allele and G12 = 2 new alleles) and VP4 (P4 = 1 new allele and P6 = 2 new alleles) genes which formed the basis of the VP7 and VP4 gene clusters, respectively. For the remaining 9 genes, 0-6 new alleles were identified for both Wa-like and DS-1-like strains. This analysis of whole genome sequences of RVA strains circulating in Benin described genetic point mutations and reassortment events as well as novel alleles. Further detailed studies on these new alleles are needed and these data can also provide a baseline for studies on RVA in the post-vaccination period.
Context: This work presents the development of a dynamic model for human lower limb motion in the sagittal plane during the gait cycle. The primary objective of this model is to serve as a powerful ...tool for the design of rehabilitation and assistive devices, such as exoskeletons, prostheses, and orthoses. It achieves this by facilitating the estimation of joint torques, the detailed analysis of kinematic variables, optimal actuator selection, and the exploration of advanced control techniques. Method: The dynamic model consists of two primary components: (1) the plant model and (2) a closed-loop controller. The plant model represents the forward dynamics of human gait and is based on a multi-mass pendulum composed of three segments of the lower limb (thigh, lower leg, and foot) and three joints (hip, knee, and ankle). It is analyzed using the Euler-Lagrange formulation and the nonlinear second-order differential equations are implemented in MATLAB’s Simulink. To reproduce reference human gait trajectories and simulate the functioning of the neuromusculoskeletal system and the central nervous system, a closed-loop PID controller is incorporated into the plant model. It is noteworthy that the scope of this dynamic model is specifically confined to the sagittal plane. Results: The dynamic model is evaluated in terms of angular displacement tracking using the relative maximum error (RME) and the root mean square error (RMSE) for reference trajectories of healthy adult male human gait as reported in the literature. The model demonstrates tracking with errors below 2.2 ° in magnitude and 3,5% for all three considered segments (thigh, lower leg, and foot). Conclusions: The quantitative results show that the dynamic model developed in this work is reliable and allows for a precise reproduction of human gait trajectories.
•Pharmaceuticals in the water of Cuernavaca and the associated risk were assessed.•Occurrence was studied by LC-MS/MS and risk was assessed by hazard quotients.•12 out of the 35 pharmaceuticals ...analyzed were present in waste- and surface water.•Concentrations measured showed the discharge of untreated wastewater into the river.•Ibuprofen, sulfamethoxazole, diclofenac, naproxen could be a risk for aquatic life.
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The present work describes the first known study to date on the occurrence of pharmaceuticals in surface water and wastewater of Cuernavaca, the capital of the state of Morelos (México). Selected pharmaceuticals (a total of 35) were extracted from the collected water samples with a generic solid phase extraction (SPE) protocol and determined in the sample extracts by means of high-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on predicted no-effect concentrations (PNECs) was also applied to estimate Hazard Quotients (HQs) for the pharmaceuticals detected in the investigated area. A total of twelve pharmaceuticals were found in the water samples analyzed, with detection frequencies above 78% and in most cases of 100%. Overall, the most abundant pharmaceuticals in surface water were the analgesic and anti-inflammatory drugs naproxen (732–4880ng/L), acetaminophen (354–4460ng/L), and diclofenac (258–1398ng/L), and the lipid regulator bezafibrate (286–2100ng/L). On the contrary, other compounds like the β-blocker atenolol and the psychiatric drug carbamazepine were found at only a few ng or tens of ng per liter in the Apatlaco River. Despite the fact that some of the most abundant compounds showed good removal (>97%) during wastewater treatment, concentrations downstream the WWTP were only slightly lower than upstream. This indicates the existence of additional inputs of untreated wastewater into the river. Based on the obtained HQ-values, the concentrations of ibuprofen, sulfamethoxazole, diclofenac and naproxen present in the river could pose a high toxicity risk for the aquatic ecosystem. These findings highlight these pharmaceuticals as relevant organic contaminants in the area of study and the need to further monitor them in order to adopt appropriate measures to safeguard the ecosystem, and eventually human health.
TRPV4 (Transient Receptor Potential Vanilloid 4) channels are activated by a wide range of stimuli, including hypotonic stress, non-noxious heat and mechanical stress and some small molecule agonists ...(e.g. phorbol ester 4α-PDD). GSK1016790A (GSK101) is a recently discovered specific small molecule agonist of TRPV4. Its effects on physical determinants of TRPV4 activity were evaluated in HeLa cells transiently transfected with TRPV4 (HeLa-TRPV4). GSK101 (10 nM) causes a TRPV4 specific Ca(2+) influx in HeLa-TRPV4 cells, but not in control transfected cells, which can be inhibited by ruthenium red and Ca(2+)-free medium more significantly at the early stage of the activation rather than the late stage, reflecting apparent partial desensitization. Western blot analysis showed that GSK101 activation did not induce an increase in TRPV4 expression at the plasma membrane, but caused an immediate and sustained downregulation of TRPV4 on the plasma membrane in HeLa-TRPV4 cells. Patch clamp analysis also revealed an early partial desensitization of the channel which was Ca(2+)-independent. FRET analysis of TRPV4 subunit assembly demonstrated that the GSK101-induced TRPV4 channel activation/desensitization was not due to alterations in homotetrameric channel formation on the plasma membrane. It is concluded that GSK101 specifically activates TRPV4 channels, leading to a rapid partial desensitization and downregulation of the channel expression on the plasma membrane. TRPV4 subunit assembly appears to occur during trafficking from the ER/Golgi to the plasma membrane and is not altered by agonist stimulation.
Vulnerable populations in developing countries need new protein sources, such as protein concentrates from accessible sources at low economic costs. The main objective of this study was at evaluating ...the nutritional quality of the protein concentrate of the legume mesquite (Prosopis juliflora), compared with the protein values of other legumes described in literature. For this purpose, flour and protein concentrates from mesquite were obtained, along with their chemical composition. Amino acid profiling was performed by high-performance liquid chromatography (HPLC). Protein quality index evaluation tests were also performed on preschool children and adults. The protein content of mesquite was found to be 68%. However, mesquite covers the requirements of essential amino acids, surpassing 31% of the protein required in adults, except for cysteine sulfur amino acids and aromatic amino acids. In other age groups such as children, mesquite had a high content of histidine, which is necessary and considered essential during infant development. According to the above, mesquite could be used as an alternative protein to produce food with high nutritional content.
Flavonolignans occur typically in
(milk thistle) fruit extract, silymarin, which contains silybin, isosilybin, silychristin, silydianin, and their 2,3-dehydroderivatives, together with other minor ...flavonoids and a polymeric phenolic fraction. Biotransformation of individual silymarin components by human microbiota was studied ex vivo, using batch incubations inoculated by fecal slurry. Samples at selected time points were analyzed by ultrahigh-performance liquid chromatography equipped with mass spectrometry. The initial experiment using a concentration of 200 mg/L showed that flavonolignans are resistant to the metabolic action of intestinal microbiota. At the lower concentration of 10 mg/L, biotransformation of flavonolignans was much slower than that of taxifolin, which was completely degraded after 16 h. While silybin, isosilybin, and 2,3-dehydrosilybin underwent mostly demethylation, silychristin was predominantly reduced. Silydianin, 2,3-dehydrosilychristin and 2,3-dehydrosilydianin were reduced, as well, and decarbonylation and cysteine conjugation proceeded. No low-molecular-weight phenolic metabolites were detected for any of the compounds tested. Strong inter-individual differences in the biotransformation profile were observed among the four fecal-material donors. In conclusion, the flavonolignans, especially at higher (pharmacological) doses, are relatively resistant to biotransformation by gut microbiota, which, however, depends strongly on the individual structures of these isomeric compounds, but also on the stool donor.
The objective of this research was to study the effect of edible coatings on the physicochemical properties of cassava chips. The oil and moisture absorption in fried cassava chips that were not ...coated and in chips that were coated with pectin and whey protein films were determined using a completely randomized experiment design with a 33 factorial arrangement. The multifactorial ANOVA analysis of variance showed that all factors had significant statistical differences for moisture loss and oil absorption (p < 0.05). The coating type, the control, and the whey protein-coated chips presented a 321% greater oil content on average at 180 °C and 180 s than the pectin-coated chips. The density, heat capacity, and thermal diffusivity had statistical differences at all temperatures (p < 0.05). The sensory analysis showed that the coating type affected all sensory parameters, except crispness, as indicated by significant statistical differences (p < 0.05). The temperature only influenced the color of the control chips, with statistical differences (p < 0.05) at all temperatures.