Nano‐encapsulated anandamide reduces inflammatory cytokines in vitro and lesion severity in a murine model of cutaneous lupus erythematosus

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Abstract

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA-NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA-NP decreased IL-6 and MCP-1 in UVB-stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA-NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL-lpr lupus murine model, twice weekly treatment of lesions with topical AEA-NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA-NP to commonly involved areas on MRL-lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA-1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential.

Reliability of field‐ and laboratory‐based assessments of health‐related fitness in preschool‐aged children

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Abstract

Objectives

Reliable measurements of health-related fitness—cardiorespiratory endurance, muscular endurance, muscular strength, body composition, and flexibility—are imperative for understanding and tracking health-related fitness from the preschool age. This study aimed to examine the test–retest reliability of field-based (i.e., sit and reach [standard and back-saver], standing long jump, grip strength); and laboratory-based (i.e., Bruce Protocol Treadmill Test, Wingate Anaerobic Test) assessments of health-related fitness in preschool aged children (4–5 years).

Methods

Forty-two typically developing children participated in both assessment time points separated by 2–3 weeks. All fitness assessments were administered individually and repeated in the same order by the same assessor. Heteroscedasticity was examined for each parameter. Intraclass correlation coefficients were calculated to assess test–retest reliability.

Results

All parameters were homoscedastic. Test–retest reliability for the field-based tests and Bruce Protocol Treadmill Test parameters were moderate to good. Test–retest reliability for the Wingate Test parameters were good to excellent for maximum pedal rate, peak power, and peak power/kg; mean power and fatigue measured at 10 and 30 s demonstrated moderate to excellent test–retest reliability.

Conclusion

The standard sit and reach, grip strength, and short-term muscle power from the Wingate test are reliable assessments of health-related fitness in preschool-aged children.

Secular trends in height, weight, and body mass index in the context of economic and political transformations in Russia from 1885 to 2021

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Abstract

Objectives

To study and analyze the impact of socio-economic factors on secular changes in height, weight, and body mass index (BMI) among Moscow's youth over the time interval from the late 19th–early 20th century to the present.

Methods

Anthropometric data, including height, weight, and BMI, were collected through surveys conducted on youths aged 17–20 years in Moscow from the 1880s for males and from the 1920s for females to the present. The dataset includes information on 6434 individuals surveyed from 2000 to 2019, as well as previously published mean values. Economic development indicators, such as gross domestic product (GDP) per capita, monthly average income per capita, and the Gini coefficient, were examined to analyze the association between secular trends in body size and socio-economic conditions.

Results

A positive secular trend in height and weight has been observed among Moscow's youth from the early 20th century to the present. Substantial increases in height occurred during the second half of the previous century, stabilizing in the 2000s. Over the analyzed period, both average body weight and BMI values showed a consistent rise. The pattern for BMI exhibited a U-shaped trend, with a decline from the 1970s to the mid-1990s, followed by a subsequent increase. Strong correlations were found between the secular changes in body size among Moscow's youth and temporal fluctuations in key socio-economic indicators, including GDP per capita, monthly average income per capita, and the Gini coefficient.

Conclusion

The study demonstrates the significant influence of socio-economic conditions on intergenerational changes in body size, as evidenced by the positive secular trend in physique indicators (height, weight, and BMI) among Moscow's youth.

Altered actin dynamics is possibly implicated in the inhibition of mechanical stimulation‐induced dermal fibroblast differentiation into myofibroblasts

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Abstract

The formation of hypertrophic scars and keloids is strongly associated with mechanical stimulation, and myofibroblasts are known to play a major role in abnormal scar formation. Wounds in patients with neurofibromatosis type 1 (NF1) become inconspicuous and lack the tendency to form abnormal scars. We hypothesized that there would be a unique response to mechanical stimulation and subsequent scar formation in NF1. To test this hypothesis, we investigated the molecular mechanisms of differentiation into myofibroblasts in NF1-derived fibroblasts and neurofibromin-depleted fibroblasts and examined actin dynamics, which is involved in fibroblast differentiation, with a focus on the pathway linking LIMK2/cofilin to actin dynamics. In normal fibroblasts, expression of α-smooth muscle actin (α-SMA), a marker of myofibroblasts, significantly increased after mechanical stimulation, whereas in NF1-derived and neurofibromin-depleted fibroblasts, α-SMA expression did not change. Phosphorylation of cofilin and subsequent actin polymerization did not increase in NF1-derived and neurofibromin-depleted fibroblasts after mechanical stimulation. Finally, in normal fibroblasts treated with Jasplakinolide, an actin stabilizer, α-SMA expression did not change after mechanical stimulation. Therefore, when neurofibromin was dysfunctional or depleted, subsequent actin polymerization did not occur in response to mechanical stimulation, which may have led to the unchanged expression of α-SMA. We believe this molecular pathway can be a potential therapeutic target for the treatment of abnormal scars.

Conditioning on the causal network prevents indirect response to selection

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Abstract

Multiple trait animal models (MTM) allow to estimate the breeding values (BV) of several traits simultaneously while accounting for genetic and environmental correlations among them. However, relationships among traits may not be reciprocal but rather causal in nature. In these cases, and given a causal network, structural equations models (SEM) arise as a more appropriate methodology. Although MTM and SEM have been shown to be parametrically equivalent, the estimated breeding value (EBV) obtained from either one or the other should be interpreted differently. In this study, we investigated the impact of using these estimates on the response to selection for a causal network comprising five different traits through a stochastic simulation experiment. Three different selection targets were assayed, involving traits located upstream, midstream and downstream this causal network. We first considered the case in which traits were causally related but not genetically correlated. The current results support our hypothesis that MTM will absorb causal relationships as genetic correlations and, consequently, change the response to selection achieved as compared with SEM. We found no differences on the response to selection when the target trait was located at the top of the causal network, but noticeable differences were detected on upstream traits when selection pressure was placed on midstream or downstream traits. We also assayed a scenario in which causal effects and genetic correlations act simultaneously and found that selection based on BVs estimated using SEM diminished the indirect response in traits upstream the causal network.

Relative contribution of season, site, scion and rootstock genotype, and susceptibility to European canker to the variability in bacterial and fungal communities in apple leaf scar tissues

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Relative contribution of season, site, scion and rootstock genotype, and susceptibility to European canker to the variability in bacterial and fungal communities in apple leaf scar tissues

Composition of endophyte around the apple leaf scars was primarily affected by season and planting location. There was a significant reduction in the community size in the spring, particularly for fungi, and species turnover between autumn and spring. Scion and rootstock genotypes had limited effects on the endophyte community. A group of resistant cultivars differed from a group of susceptible ones in the relative abundance of many bacterial and fungal OTUs, including OTUs from Sphingomonas, Methylobacterium, Vishniacozyma and Rhodotorula babjevae.


Abstract

Neonectria ditissima infects apple trees through wounds, causing European canker. In the UK, the most important entry site for N. ditissima is leaf scar. Specific apple endophytes may contribute to cultivar resistance/tolerance to the pathogen. We assessed the relative effect of location, sampling time (season), and rootstock/scion genotype on bacterial and fungal endophyte communities in the apple leaf scar tissues of current-season extension shoots and identified Operational Taxonomic Units (OTUs) with differential abundance between canker resistant and susceptible scions, and between rootstocks. Leaf scar tissues were sampled from two orchards at three times (10/2018, 06/2019 and 10/2019) for eight scion cultivars, each grafted onto two rootstocks, for profiling 16S and ITS rRNA regions. Endophyte composition was primarily affected by season (autumn vs. spring) and location (sites and blocks within site). There was a significant reduction in the community size in the spring, particularly for fungi, and species turnover between autumn and spring. This seasonal dynamics suggest that to protect leaf scars from N. ditissima infection in the autumn specific endophytes suppressing canker may have to be augmented annually around the leaf-fall time. Scion and rootstock genotypes had limited effects on the endophyte community. A group of resistant cultivars differed from a group of susceptible ones in the relative abundance of many bacterial and fungal OTUs, most of which had low reads numbers. Nevertheless, several OTUs with high reads numbers differed in their relative abundance between resistant and susceptible scions, including OTUs from Sphingomonas, Methylobacterium, Vishniacozyma and Rhodotorula babjevae, and warrant further investigation for their potential role in host resistance/tolerance against N. ditissima.

Compared to antibiotic, feeding peony byproducts can improve growth performance, rumen fermentation, slaughter parameters, and meat quality of lambs

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Abstract

Our objective was to determine effects of feeding lamb's peony byproducts, including stem and leaves (PSL), root (PR), and seeds meal (PSM), on growth, rumen fermentation, slaughter parameters, and meat quality. Sixty-four lambs (14.0 ± 2.1 kg) were allocated into eight treatments based on BW: no additives (CON), 0.15% aureomycin (CONA), low/high levels of PSL (5%/10% PSL replaced 5%/10% Chinese hay), PR (basal diet with 0.5%/1.0% PR), PSM (5%/10% PSM replaced 5%/10% soybean meal). Growth, digestibility, and rumen fermentation had dose responses whereas slaughter parameters, meat quality, or amino acids indexes were not. Peony byproducts increased DMI (p < 0.001) compared to CON, but higher levels were more advantageous (p = 0.003). However, low levels of peony byproducts decreased the NH3-N concentration, but increased total volatile fatty acids mole percent more than high levels of that (p < 0.001). All peony byproducts increased dressing percentage (p < 0.05), increased pH and tenderness than CON (p < 0.05). In addition, PSL and PSM improved amino acid profiles of meat compared to CON, and were even better than CONA (p < 0.05). Therefore, peony byproducts not only improved animal growth but also reduced the frequency of antibiotic use in animal feeding.

Effects of exercise on whole‐blood transcriptome profile in children with overweight/obesity

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Abstract

Background

The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in childhood. We set out to investigate the effects of a 20-week exercise intervention on whole-blood transcriptome profile (RNA-seq) in children with overweight/obesity.

Methods

Twenty-four children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n = 10), or to a no-exercise control group (n = 14). Whole-blood transcriptome profile was analyzed using RNA-seq by STRT technique with GlobinLock technology.

Results

Following the 20-week exercise intervention program, 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value <0.05), while after multiple correction, no significant difference between exercise and control groups persisted in gene expression profiles (FDR >0.05). Genes enriched in GO processes and molecular pathways showed different immune response in boys (antigen processing and presentation, infections, and T cell receptor complex) and in girls (Fc epsilon RI signaling pathway) (FDR <0.05).

Conclusion

These results suggest that 20-week exercise intervention program alters the molecular pathways involved in immune processes in children with overweight/obesity.