Possibly like all cells, those in the ovary, e.g., granulosa cells and oocytes (less is known about melatonin synthesis by the testes or spermatogenic cells), synthesize melatonin which is used locally to combat free radicals and reactive nitrogen species which would otherwise cause oxidative/nitrosative stress to these critically important cells. Oxidative damage to the oocyte, zygote, blastocyst, etc., results in an abnormal fetus which is either sloughed or gives rise to an unhealthy offspring. The importance of the protection of the gametes (both oocytes and sperm) from oxidative molecular mutilation cannot be overstated. Fortunately, as a highly effective free radical scavenger and indirect antioxidant (by upregulating antioxidant enzyme), locally-produced melatonin is in the optimal location to protect the reproductive system from such damage.The epidermal growth factor receptor (EGFR) is a pleiotropic glycoprotein which plays a role in regulating cell proliferation, migration and differentiation. However, to date little is known about its functions in crustaceans. In this study, we successfully identified SpEGFR from mud crab Scylla paramamosain. RT-PCR result showed that SpEGFR was widely distributed in all tested tissues and highly expressed in ovary. In situ hybridization revealed that SpEGFR mainly localized in oocyte perinuclear region with notably obvious signals. In vitro experiments showed that the expression of SpVgR and SpCyclin B in ovary explants from late vitellogenic stage crabs (summer) were significantly increased when treated with 1 nM human EGF (hEGF) for 1 h, while there was no obvious change towards SpEGFR. Interestingly, as for winter crab at the same vitellogenic stage, the expression of SpVgR and SpCyclin B in ovary explants did not show significant increase until treated with higher concentration of 10 nM hEGF and longer incubation time of 12 h. In addition, the hEGF-induced effect could be suppressed by pre-treated with EGFR inhibitor AG1478 and PD153035, respectively, which further indicated that EGF-EGFR pathway played a vital role in ovarian development in mud crab. In conclusion, SpEGFR might promote ovarian development by stimulating the expression of SpVgR and SpCyclin B under hEGF-induced treatment. The different physiological response to hEGF in the same vitellogenic stage crabs between summer and winter might be attributed to the changes in metabolism and physiological sensitivity.Glucocorticoid hormones (GCs) are central mediators of metabolism and the response to challenges. Because circulating GC levels increase in response to challenges, within-population variation in GCs could reflect among-individual variation in condition or experience. At the same time, individual variation in GC regulation could have causal effects on energetic balance or stress coping capacity in ways that influence fitness. Although a number of studies in vertebrates have tested whether variation in GCs among individuals predicts components of fitness, it is not clear whether there are consistent patterns across taxa. Here we present the first phylogenetic meta-analysis testing whether variation in GCs is associated with survival and reproductive success across vertebrates. At the same time, we introduce and test predictions about a potentially important mediator of GC-fitness relationships life history context. We suggest that strong context-dependence in the fitness benefit of maintaining elevated GCs coulss relationships can be strongly context dependent, and suggest that incorporating life history may be particularly important for understanding GC-survival relationships.Estradiol-17β (E2) promotes the transcription of vitellogenin (Vtg) via nuclear estrogen receptor (ER). Three Vtg (VtgAa, VtgAb, and VtgC) and ER subtypes (ERα, ERβ1, and ERβ2) have been reported in perciform fish; however, the relationship between the transcriptional regulation of Vtg and ER subtypes remains unclear. Molecular characterization was performed and the expression profiles of vtg and er subtypes were investigated to elucidate mechanisms of synthesis of vtg subtypes in yellowtail, Seriola quinqueradiata. Primary structures and promoter regions were revealed in three subtypes of vtg and er, and all the vtg subtypes and erα were presumed to be estrogen-responsive genes. When all vtg subtypes were expressed significantly in the liver, hepatic expression levels of all the er subtypes also increased. Conversely, although plasma E2 concentrations did not change significantly, the concentrations were high at the same time. Hepatic expression levels of all the vtg subtypes were highly correlated with hepatic erα, rather than with hepatic erβ subtypes and plasma E2. A high positive correlation was also observed between erβ1 and β2, which seemed to be highly expressed at the pre- and late-vitellogenic stages. The results of the present study suggest that the transcription of the three vtg subtypes are regulated by three ER subtypes jointly, and ERα is the key transcription factor regulating the three vtg subtypes in yellowtail.The mitosis-associated protein aurora kinase A (AURKA) regulates the maturation of germ cells. We have previously reported using transcriptome analysis that AURKA is expressed in yak testes. Although Tibetan sheep possess an immense economic value, their reproductive rate is low. Herein, the expression and functions of AURKA in the hypothalamus-pituitary-testicular (HPT) axis in Tibetan sheep from Tianzhu were investigated. The cDNA sequence of sheep AURKA was cloned and bioinformatics techniques were used to predict its structure. Tissue expression of AURKA was determined by qPCR, immunoblotting, immunostaining, and immunohistochemistry. The AURKA coding sequence was found to be 1218 bp in length, encoding a 405-amino acid polypeptide chain. Furthermore, the highest sequence similarity of AURKA with the corresponding sequence in other species was seen in goat and cattle; the least degree of similarity was seen in the domestic cat. In addition, AURKA expression was elevated in the testes compared to that in the hypothalamus and pituitary (p less then 0.01). Moreover, AURKA was mainly localized in the hypothalamic paraventricular nucleus (magnocellular), chromophobe cells of the pituitary, and spermatogenic cells of the testis. These results indicated that AURKA might participate in sheep reproductive regulation, thus providing a reference for the study of AURKA function in the reproductive process of Tibetan sheep from Tianzhu.

There has been an increasing trend towards the ulcerative colitis (UC) incidence worldwide. The present study aimed to explore novel biomarkers and potential therapeutic agents for UC.

Differentially expressed genes (DEGs) among UC and healthy control samples were identified by GEO2R online tool. Functional analysis was performed and protein-protein interaction networks were constructed. The hub genes were explored by Cytoscape, and quantitative real-time-PCR (qRT-PCR) was used to valid their expression in clinical samples. ImmuCellAI was utilized to analyze the fraction of 24 types of immune cells. The L1000 platform was applied to determine potential agents for UC treatment. The dextran sulfate sodium (DSS)-induced colitis model was used to identify the therapeutic effect of meclofenamic acid.

A total of 270 DEGs were identified among UC and healthy control samples. Functional analysis indicated that the DEGs were primarily enriched in several immune response and digestion pathways. A proportion of 18 immune-cell types was found to be significantly altered between UC and healthy control samples. 10 compounds were predicted to have therapeutic potentials for treating UC. Among them, we selected meclofenamic acid to identify its therapeutic effect on UC treatment by animal experiments.

The current study comprehensively analyzed the DEGs and immune infiltration in UC, as well as screened for potential agents for UC treatment.

The current study comprehensively analyzed the DEGs and immune infiltration in UC, as well as screened for potential agents for UC treatment.

Ionizing radiation (IR) induces injuries to the hematopoietic and intestinal systems, which are the leading cause of death. Baicalein, a plant-derived flavonoid, shows anti-oxidative stress, anti-apoptosis, anti-inflammation effects in many diseases. In this study, we evaluated the effects and mechanism of baicalein on IR induced intestinal and hematopoietic injuries.

Mice were divided into three groups Control, IR and IR+Baicalein. All of mice were intraperitoneally administered with 100mg/kg baicalein or normal saline for 1h before IR, and then a day post-IR. The changes in intestinal structure, function and molecular expression were observed by pathological experiments and western blot. 16S rRNA gene sequencing was performed to analyze gut microbiota and further predicted metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hematopoietic function was evaluated by peripheral blood cells count and by flow cytometry analysis of hematopoietic cells composition.

Baicalein improved intestinal structure and the ability of proliferation and regeneration after mice exposed to IR, in which the rebalance of gut microbial composition played an important role. KEGG results showed that p53-related apoptotic pathways played important roles in the composition changes of gut microbiota. Then we observed that baicalein inhibited the activation of p53 and p53 mediated mitochondrial apoptosis and death receptor apoptosis in the intestine. In addition, IR induced injuries to hematopoietic system also could be ameliorated by baicalein.

These results provide new insights into the mechanism of baicalein and support the potential of baicalein as a radioprotective medicine.

These results provide new insights into the mechanism of baicalein and support the potential of baicalein as a radioprotective medicine.Acute kidney injury (AKI) is an abrupt and usually reversible decline in renal function. AKI is considered one of the main drawbacks of the use of gentamicin that critically limits its clinical use. In this study, pirfenidone, an oral antifibrotic drug, was given to rats (200 mg/kg, p.o., daily) for seven days alone before the initiation of gentamicin treatment and continued for seven days alongside daily gentamicin injections. In gentamicin group, gentamicin was given to Wistar rats (100 mg/kg, i.p., daily) for seven days to induce AKI. Pirfenidone managed to alleviate gentamicin-induced AKI by improving kidney function parameters including serum creatinine, blood urea nitrogen (BUN), proteinuria, relative kidney-to-body weight ratio and creatinine clearance. Pirfenidone decreased cytotoxicity induced by gentamicin by decreasing lactate dehydrogenase (LDH) activity and improving histologic picture of tubules and glomeruli. Pirfenidone also alleviated oxidative stress induced by gentamicin by reducing malondialdehyde (MDA) and elevating reduced glutathione (GSH). Pirfenidone prevented the upregulated inflammasome pathway markers in the kidney. It succeeded in decreasing toll like recpetor-4 (TLR4), nuclear factor-kappa B (NF-κB), nucleotide-binding oligomerization domain [NOD]-like pyrin domain containing protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β) and IL-18 levels. Additionally, Pirfenidone caused a decrease in macrophage infiltration displayed by reduction in renal monocyte chemoattractant protein-1 (MCP-1) levels. To sum up, pirfenidone can effectively mitigate gentamicin-induced AKI by inhibiting oxidative stress, macrophage infiltration and inflammasome-dependent NLRP3 pathway-induced inflammation.