Eriocaulon buergerianum extract protects PC12 cells and neurons in zebrafish against 6-hydroxydopamine-induced damage

<p>Abstract</p> <p>Background</p> <p><it>Ericaulon buergerianum </it>(<it>Gujingcao</it>) is an ophthalmic, anti-inflammatory and antimicrobial Chinese medicinal herb. This study aims to investigate the neuroprotective effects of <it>Ericaulon buergerianum </it>ethanol extract (EBE) and to elucidate its underlying action mechanism.</p> <p>Methods</p> <p>The viability of dopaminergic (DA) neuron in zebrafish was examined by anti-tyrosine hydroxylase (TH) immunostaining. The locomotor activity of zebrafish was assessed with a digital video tracking system. The viability and cellular damage of the PC12 cells were determined by MTT and LDH assays respectively. The nuclear morphological changes in apoptotic cells were evaluated with DNA staining by Hoechst 33342 dye. Intracellular nitric oxide (NO) was quantified by DAF-FM diacetate staining. The expression of inducible nitric oxide synthase (iNOS) was determined by Western blot.</p> <p>Results</p> <p>EBE inhibited the 6-OHDA-induced decrease in total distance of movement in zebrafish. Pretreatments of EBE (25, 50, 100 and 200 μg/ml) increased the viability of 6-OHDA-damaged PC12 cells in a dose dependent manner. Protection against 6-OHDA-induced nuclear fragmentation and accumulation of apoptotic bodies was also observed in EBE pretreated cells. Anti-oxidative (inhibition of NO production and iNOS expression in PC12 cells <it>in vitro</it>) activities of EBE are related to its neuroprotective effects in 6-OHDA-induced DA neuron damage.</p> <p>Conclusion</p> <p>EBE exhibited significant neuroprotective activities in zebrafish, including recovery of dopaminergic neuron loss caused by 6-OHDA in a dose-dependent manner <it>in vivo</it>, inhibition of 6-OHDA-induced decrease of total distance in movement in zebrafish. The iNOS-NO pathway may be involved.</p

Decoding the mystery between hyperuricemia and atrial fibrillation: new causal links through mediating proteomics

BackgroundAtrial fibrillation (AF), the most common cardiac arrhythmia, is associated with high incidence and mortality rates. Recent studies have confirmed a close correlation between hyperuricemia and the onset of AF, though the mechanisms remain unclear. Consequently, this study employs Mendelian randomization based on proteomics and mediation analysis to investigate the potential mechanisms by which hyperuricemia induces AF.MethodsA two-step mediation MR analysis was conducted to determine whether plasma proteins mediate atrial fibrillation induced by serum urate. The Reactome database was subsequently utilized to analyze the list of significant mediating plasma proteins to identify enriched pathways.ResultsMediation Mendelian randomization analysis suggested that hyperuricemia may promote the development of atrial fibrillation (AF) through 17 plasma proteins, includeing hepatocyte nuclear factor 4-alpha (HNF4α), identified as key mediators. Subsequent enrichment analysis of these proteins revealed 9 metabolic or signaling pathways potentially involved in this pathological process. Central mediator proteins such as HNF4α appear to drive AF through metabolic and inflammatory pathways.ConclusionThere is a close correlation between hyperuricemia and the onset of atrial fibrillation

Effects of maternal dietary heme Fe supplementation on liver iron levels and expression of iron regulatory genes in newborn piglets

Iron deficiency in sows has been demonstrated to have a detrimental effect on porcine fetal growth and development, as well as on the reproductive performance of sows. The placental barrier of sows restricts the transportation of inorganic iron to the fetus, resulting in iron deficiency anemia in neonatal piglets and consequently leading to slow growth. The purpose of this study is to explore the effect of heme Fe on iron metabolism in pregnant sows. Ninety-six multiparous Landrace × Yorkshire (LY) sows (weight 235 ± 15kg) with similar litter size and feeding management were randomly divided into four treatment groups: control group (supplemented with 400 mg/kg), iron deficiency group (with no added FeSO4), heme Fe group (supplemented with 140 mg/kg), and glycine Fe group (supplemented with 470 mg/kg). Iron supplementation lasted from the second trimester (day 30) to day 114 before delivery. In this study, the production performance of sows, the iron content in sow placentas, and in the livers, spleens, placenta and colostrum of newborn piglets, as well as the hemoglobin(HGB) level, the iron regulation parameters in the serum of newborn piglets and the iron regulation genes in the livers and placentas were measured. The results showed that: (1) The number of live births and the average birth weight of piglets in the heme Fe group were 14.8% and 6.33% higher than those in the control group, respectively(P &lt; 0.01). Compared with FeSO4 and glycine Fe, heme Fe improved the production performance of sows. (2) In the heme Fe group, the iron content in colostrum was significantly higher than in the control group (1.27-fold) and glycine Fe group (0.45-fold), while the iron content in the livers of newborn piglets increased by 30.38% and 14.61% compared to the control and glycine Fe groups, respectively (P &lt; 0.01). These results suggest that heme Fe significantly facilitates iron transport in sows, particularly enhancing its deposition in colostrum and neonatal livers. This effect may be attributed to the upregulated expression of heme oxygenase 1(HO-1) gene in the placenta, which enhances the uptake and transport of heme Fe, thereby increasing fetal iron acquisition.(3) In the liver and placentas of sows in the deficiency group, the expression of hepcidin was decreased, while the expressions of transferrin receptor 1 (tfr1), feline leukemia virus subgroup C receptor 1(Flvcr1) and transferrin were increased (P &lt; 0.01). In addition, the gene expression level of HO-1 in the heme Fe group of liver was significantly higher compared to that in the control group (1.85-fold), the iron deficiency group (2.99-fold), and the iron glycinate group (1.67-fold). In conclusion, maternal heme Fe supplements have a significant impact on iron storage in neonatal piglets and are helpful for preventing iron deficiency in newborn piglets

FOXL2 and DMRT1L Are Yin and Yang Genes for Determining Timing of Sex Differentiation in the Bivalve Mollusk Patinopecten yessoensis

Sex determination and differentiation have long been a research hotspot in metazoans. However, little is known about when and how sex differentiation occurs in most mollusks. In this study, we conducted a combined morphological and molecular study on sex differentiation in the Yesso scallop Patinopecten yessoensis. Histological examination on gonads from 5- to 13-month-old juveniles revealed that the morphological sex differentiation occurred at 10 months of age. To determine the onset of molecular sex differentiation, molecular markers were screened for early identification of sex. The gonadal expression profiles of eight candidate genes for sex determination or differentiation showed that only two genes displayed sexually dimorphic expression, with FOXL2 being abundant in ovaries and DMRT1L in testes. In situ hybridization revealed that both of them were detected in germ cells and follicle cells. We therefore developed LOG10(DMRT1L/FOXL2) for scallop sex identification and confirmed its feasibility in differentiated individuals. By tracing its changes in 5- to 13-month-old juveniles, molecular sex differentiation time was determined: some scallops differentiate early in September when they are 7 months old, and some do late in December when they are 10 months old. Two kinds of coexpression patterns were found between FOXL2 and DMRT1L: expected antagonism after differentiation and unexpected coordination before differentiation. Our results revealed that scallop sex differentiation co-occurs with the formation of follicles, and molecular sex differentiation is established prior to morphological sex differentiation. Our study will assist in a better understanding of the molecular mechanism underlying bivalve sex differentiation

Identification and characterization of gonadotropin-releasing hormone (GnRH) in Zhikong scallop Chlamys farreri during gonadal development

Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on neuroendocrine control of gonadal function, such as the function of GnRH during gonadal development is limited. In this study, we investigated the morphology and structure of the nerve ganglia of Zhikong scallop Chlamys farreri by physiological and histological observations. We also cloned the ORF and studied the expression patterns of GnRH in the scallop. Tissue expression analysis showed that GnRH was highly expressed in parietovisceral ganglion (PVG). The in situ hybridization result further confirmed that GnRH mRNA only distributed in some good-sized neurons in the posterior lobe (PL) and some pint-sized neurons in the lateral lobe (LL). In addition, by examining the expression of GnRH during gonadal development in ganglia, we found GnRH displayed higher expression in the female scallops, and showed significant high expression at the growing stage of female scallops in PVG. This study would contribute to gaining insight into the mechanism underlying reproduction regulation by GnRH in the scallop and help to provide a better understanding of reproductive neuroendocrine in mollusks