High-Fat Diet-Induced Fatty Liver Is Associated with Immunosuppressive Response during Sepsis in Mice

High-fat diet-induced fatty liver is an indolent and chronic disease accompanied by immune dysfunction and metabolic disturbances involving numerous biological pathways. This study investigated how this abnormal metabolic disorder influences sepsis in mice. Mice were fed with normal chow (NC) or high-fat diet (HFD), and palmitic acid (PA) was used to treat hepatocytes to mimic fat accumulation in vitro. Lipopolysaccharide (LPS) was used to induce sepsis and related immune responses. Mice fed on a high-fat diet displayed higher mortality and more severe liver damage but compromised immunoreaction. The supernatant from PA-treated primary hepatocytes markedly diminished the inflammatory cytokine expression of macrophages after LPS stimulation, which showed a state of immunosuppression. Metabolomics analysis indicated the level of many key metabolites with possible roles in immunoreaction was altered in the HFD and PA groups compared with corresponding controls; specifically, β-hydroxybutyric acid (BHB) showed an immunosuppressive effect on Raw264.7 cells during the LPS stimulation. Transcriptomic analysis suggested that several differential signaling pathways may be associated with the alteration of immune function between the NC and HFD groups, as well as in the in vitro model. Our study suggests that the consumption of HFD may alter the hepatic metabolic profile, and that certain metabolites may remold the immune system to immunosuppressive state in the context of sepsis.

An Evolutionary Conserved Signaling Network Between Mouse and Human Underlies the Differential Osteoskeletal Potential of Frontal and Parietal Calvarial Bones

The mammalian calvarial vault is an ancient and highly conserved structure among species, however, the mechanisms governing osteogenesis of the calvarial vault and how they might be conserved across mammalian species remain unclear. The aim of this study was to determine if regional differences in osteogenic potential of the calvarial vault, first described in mice, extend to humans. We derived human frontal and parietal osteoblasts from fetal calvarial tissue, demonstrating enhanced osteogenic potential both in vitro and in vivo of human frontal derived osteoblasts compared to parietal derived osteoblasts. Furthermore, we found shared differential signaling patterns in the canonical WNT, TGF-β, BMP, and FGF pathways previously described in the mouse to govern these regional differences in osteogenic potential. Taken together, our findings unveil evolutionary conserved similarities both at functional and molecular level between the mouse and human calvarial bones, providing further support that studies employing mouse models, are suitable for translational studies to human.

Roles of Brassinosteroids in Mitigating Heat Stress Damage in Cereal Crops

Heat stress causes huge losses in the yield of cereal crops. Temperature influences the rate of plant metabolic and developmental processes that ultimately determine the production of grains, with high temperatures causing a reduction in grain yield and quality. To ensure continued food security, the tolerance of high temperature is rapidly becoming necessary. Brassinosteroids (BR) are a class of plant hormones that impact tolerance to various biotic and abiotic stresses and regulate cereal growth and fertility. Fine-tuning the action of BR has the potential to increase cereals’ tolerance and acclimation to heat stress and maintain yields. Mechanistically, exogenous applications of BR protect yields through amplifying responses to heat stress and rescuing the expression of growth promoters. Varied BR compounds and differential signaling mechanisms across cereals point to a diversity of mechanisms that can be leveraged to mitigate heat stress. Further, hormone transport and BR interaction with other molecules in plants may be critical to utilizing BR as protective agrochemicals against heat stress. Understanding the interplay between heat stress responses, growth processes and hormone signaling may lead us to a comprehensive dogma of how to tune BR application for optimizing cereal growth under challenging environments in the field.

Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies

Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, and cancer progression. Ultimately, we review the preclinical and clinical uses of Autotaxin, LPA, and its receptors as therapeutic targets, approaching the most recent data of promising molecules modulating both LPA production and signaling. This review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.

Kallistatin in Follicular Fluid of Women with Endometriosis and Its Correlation with IVF Outcome

Background: Endometriosis (EM) affects 10% of women in reproductive age and alters fertility. Its management is still debated notably the timing of surgery and ART in infertility. Kallistatin (KS) is an endogenous protein that regulates differential signaling pathways and biological functions. However, the function and the underlying molecular mechanism in endometriosis and its correlation with IVF outcome have not been determined. The purpose of this study was to evaluate KS concentrations in follicular fluid of women with EM and controls women without EM who underwent IVF with embryo transfer (IVF–ET). Methods: Follicular fluid KS concentrations from 40 patients with EM and 40 non-EM patients were measured by ELISA. Results: Compared with the non-EM patients, patients with EM had lower KS levels in follicular fluid (281.67±104.60 pg/ml vs. 490.70 ±216.33pg/ml). The rates of fertilization(61.64±22.42% vs. 71.00±24.39%) , available embryo (45.96±19.83% vs.50.61±26.26%) and top-quality embryo(12.71±21.01% vs.16.04±16.87%) were significantly lower in the EM group than in the control group. The KS concentrations in the follicular fluid of women who conceived consequent to the treatment were significantly higher than those from women who did not in the combined EM and control groups.Conclusions:The present results indicate that the KS concentration in follicular fluid could be used as a predictor for IVF–ET outcomes. This may contribute to the pathologic mechanism responsible for the poor outcome of IVF in patients with EM.