Citrus bioactive compounds improve bone quality and plasma antioxidant activity in orchidectomized rats

BackgroundsWe reported that citrus consumption improves bone quality in orchidectomized male rats. In the present study, effects of feeding citrus bioactive compounds and crude extract on bone quality in orchidectomized rats were evaluated.MethodsSeventy 90-days-old male rats were randomly assigned to five groups for 60 days of feeding study. The treatment groups were SHAM-control, orchidectomy (ORX), ORX+crude extract, ORX+limonin, and ORX+naringin. At termination, animals were euthanized, blood was collected for the plasma antioxidant status. Bone resorption and bone formation markers in the blood and urine were evaluated. Bone quality in the femur and the 5th lumbar and the total calcium concentration in the bones and excreta were evaluated.ResultsOrchidectomy lowered (p<0.05) plasma antioxidant capacity, bone quality, and bone calcium; elevated (p<0.05) TRAP, deoxypyridinoline (DPD), and calcium excretion; and did not change the plasma IGF-I in comparison to the SHAM group. The citrus crude extract or the purified bioactive compounds increased (p<0.05) the plasma antioxidant status, plasma IGF-I, and bone density, preserved (p<0.05) the concentration of calcium in the femur and in the 5th lumbar, and numerically improved bone strength. The crude extract and the bioactive compounds decreased (p<0.05) fecal excretion of calcium, numerically lowered the urinary excretion of calcium, and suppressed (p<0.05) the plasma TRAP activity without affecting (p>0.1) urinary excretion of DPD in comparison to the ORX group.ConclusionsPotential benefit of the citrus crude extract and its bioactive compounds on bone quality appears to preserve bone calcium concentration and increase antioxidant status.     

A dynamic structural model for estrogen receptor-alpha activation by ligands,emphasizing the role of interactions between distant A and E domains

The functional interplay between different domains of estrogen receptor-alpha (ERalpha, NR3A1) is responsible for the overall properties of the full-length protein. We previously identified an interaction between the N-terminal A and C-terminal domains, which we demonstrate here to repress ligand-independent transactivation and transrepression abilities of ERalpha. Using targeted mutations based on ERalpha structural models, we determine the basis for this interaction that defines a regulatory interplay between ERalpha A domain, corepressors, and ERalpha Helix 12 for binding to the same C-terminal surface. We propose a dynamic model where binding of different ligands influences the A/D-F domain interaction and results in specific functional outcomes. This model gives insights into the dynamic properties of full-length ERalpha and into the structure of unliganded ERalpha.     

EW-7197 prevents ulcerative colitis-associated fibrosis and inflammation

EW-7197 is a transforming growth factor-β type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.     

Backcross-breeding and doubled-haploid facilitated introgression of stripe rust resistance in bread wheat

Stripe rust caused by the fungus Puccinia striiformis f. sp. tritici (Pst) may decrease wheat yield significantly in severe outbreaks. The most cost-effective and environmentally friendly approach to reduce yield losses due to rust diseases is deployment of effective resistant genes in wheat cultivars. The causal agents evolve and may break existing resistant sources as well. Therefore, long-term conventional breeding strategies and the ongoing evolution of pathogen populations in the region would put the success of breeding programmes at risk so that there is always a need for speeding up the process of germplasm enhancement through production of doubled-haploid breeding materials. In this study, we aimed at introgression of stripe rust resistance trait from three genotypes (Flanders, Martonvasar-17 (MV17) and Bersee) into a widely adapted cultivar “Ghods”. Positively selected F2BC² progenies of three backcrossing schemas, i.e. (i) Flanders/3^*Ghods; (ii) Ghods^*3/MV17; and (iii) Hybride-de-bersee/3^*Ghods, were used to produce three small-size doubled-haploid populations via wheat × Maize pollination methodology. The doubled-haploid populations were examined against two predominantly isolates of P. striiformis f. sp. tritici (Pst) i.e. 6E134A⁺ and 6E2A⁺Yr27⁺ and the screening revealed that 44 and 52 of the progenies are resistant to the above-mentioned isolates, respectively. Field data have shown that the stripe rust resistance doubled-haploid germplasm are comparable to local check cultivars in yield and earliness.     

Increasing maternal age of blastocyst affects on efficient derivation and behavior of mouse embryonic stem cells

Mouse embryonic stem cells (mESCs) have the capability to undergo unlimited cell division and differentiate into derivatives of all three embryonic germ layers. These fundamental features enable mESCs to potentially be appropriate, efficient models for biological and medical research. Therefore, it is essential to produce high-performance mESCs. In the current study, we have produced mESCs from blastocysts that developed from fertilized oocytes of 2 (2-C57)-, 4 (4-C57)-, and 6 (6-C57)-month-old C57BL/6 mice. A comparison of isolated stem cells was done from the viewpoint of the efficiency of mESC derivation, self-renewal, and their differentiation capacity. All generated mESCs showed a similar expression of the molecular markers protein of pluripotency and AP activity. In the 3i medium, there was a significant decrease in undifferentiated marker genes expression in the 2-C57 cells compared with the other two groups ( P < 0.05) but developmental genes significantly increased in the 4-C57 and 6-C57 cells compared with the 2-C57 cells ( P < 0.05). The differentiation capacity into three germ layers through the embryoid body formation and percentage of cell lines with normal numbers of chromosomes reduced with increased maternal age. The highest DT and highest percentage of cells in the S phase belonged to 2-C57 cells. These data demonstrated that blastocysts which developed from fertilized oocytes of 2-, 4-, and 6-month-old C57BL/6 mice can generate pluripotent stem cells, and suggested that both the efficiency of mESC isolation and the behavior of these isolated mESCs including pluripotency, self-renewal, cell cycle, and DT changed with increasing maternal age.     

Variations in rest-activity rhythm are associated with clinically measured disease severity in Parkinson’s disease

ABSTRACT

The continuous, longitudinal nature of accelerometry monitoring is well-suited to capturing the regular 24-hour oscillations in human activity across the day, the cumulative effect of our circadian rhythm and behavior. Disruption of the circadian rhythm in turn disrupts rest-activity rhythms. Although circadian disruption is a major feature of Parkinson’s disease (PD), rest-activity rhythms and their relationship with disease severity have not been well characterized in PD. 13 PD participants (Hoehn & Yahr Stage [H&Y] 1–3) wore a Philips Actiwatch Spectrum PRO continuously for two separate weeks. Rest-activity rhythms were quantified by fitting an oscillating 24-hour cosinor model to each participant-day of activity data. One-way ANOVAs adjusted for demographics revealed significant variation in the amount (MESOR, F = 12.76, p < .01), range (Amplitude, F = 9.62, p < .01), and timing (Acrophase, F = 2.7, p = .05) of activity across H&Y Stages. Those with higher H&Y Stages were significantly more likely to be active later in the day, where-as those who shifted between H&Y Stages during the study were significantly more active than those who did not change H&Y Stage. Being active later in the day was also significantly associated with higher scores on the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Section III (motor symptom severity, p = .02), Section II (self-reported impact of motor symptoms on daily living, p = .01), and Total Score (p = .01) in an adjusted linear regression model; significant associations between MDS-UPDRS scores and activity levels were observed only in the unadjusted model. These findings demonstrate that continuous actigraphy is capable of detecting rest-activity disruption in PD, and provides preliminary evidence that rest-activity rhythms are associated with motor symptom severity and H&Y Stage.     

Radiolaires mésozoïques de la formation de Kermanshah (Iran)

Radiolarites are one of the characteristic facies of the Tethyan Mesozoic realm. In western Iran, the Kermanshah radiolarites belong to a vast siliceous complex characteristic of the Mesozoic rocks of the Tethys region. These siliceous sequences are associated either with ophiolitic outcrops, which allow us to date them, or to sedimentary sequences that were deposited in a long and narrow basin in an intertropical zone, which benefited from the nutritional content of upwellings driven by monsoons. This basin extended from the Hawasina series (Oman) in the south, continued northward into the series of Pichakun (South Iran) and Kermanshah (western Iran) and ended with the Kocali series (Turkey). Radiolarites were dated in these different parts of the basin except in Kermanshah. The present work fills this gap and reveals that several levels can be dated by radiolarians from the Lower Pliensbachian, for the oldest ones, up until the Turonian for the youngest.