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Sea urchin (Mesocentrotus nudus) is a commercially significant mariculture species, with its gonads being the exclusive edible parts for humans. Identifying sex-related genes is an effective approach for elucidating the underlying molecular mechanisms of gonad development in sea urchins. Some cytochrome P450 (CYP) superfamily members play critical roles in sex differentiation, steroid hormone biosynthesis, and ovarian steroidogenesis. In the present study, we identified 83 CYPs assigned to 17 families from the gonadal transcriptomic data of M. nudus, with most CYPs clustering within the CYP 2 family branches. Furthermore, we identified 11 gender-biased CYPs, including CYP 17A1, CYP 2, CYP 3A24, CYP 4V2, and CYP 46A1, as well as 11 CYPs related to steroid hormone biosynthesis, including CYP 1A1, CYP 1A5, CYP 3, and CYP 17A1. The expression patterns of those candidate sex-related CYP genes were also analyzed. The findings lay the foundation for further investigating the role of CYPs in the endogenous synthesis of sex steroids, offering valuable insights into the molecular mechanisms underlying sex differentiation in sea urchins.

Members of the Doublesex and Mab-3-related transcription factor (Dmrt) gene family handle various vital functions in several biological processes, including sex determination/differentiation and gonad development. Dmrt1 and Sox9 (SoxE in invertebrates) exhibit a very conserved interaction function during testis formation in vertebrates. However, the dynamic expression pattern and functional roles of the Dmrt gene family and SoxE have not yet been identified in any echinoderm species. Herein, five members of the Dmrt gene family (Dmrt1, 2, 3a, 3b and 5) and the ancestor SoxE gene were identified from the genome of Apostichopus japonicus. Expression studies of Dmrt family genes and SoxE in different tissues of adult males and females revealed different expression patterns of each gene. Transcription of Dmrt2, Dmrt3a and Dmrt3b was higher expressed in the tube feet and coelomocytes instead of in gonadal tissues. The expression of Dmrt1 was found to be sustained throughout spermatogenesis. Knocking-down of Dmrt1 by means of RNA interference (RNAi) led to the downregulation of SoxE and upregulation of the ovarian regulator foxl2 in the testes. This indicates that Dmrt1 may be a positive regulator of SoxE and may play a role in the development of the testes in the sea cucumber. The expression level of SoxE was higher in the ovaries than in the testes, and knocking down of SoxE by RNAi reduced SoxE and Dmrt1 expression but conversely increased the expression of foxl2 in the testes. In summary, this study indicates that Dmrt1 and SoxE are indispensable for testicular differentiation, and SoxE might play a functional role during ovary differentiation in the sea cucumber.

A major type of serious mood disorder, depression is currently a widespread and easily overlooked psychological illness. With the low side effects of natural products in the treatment of diseases becoming the pursuit of new antidepressants, natural Chinese medicine products have been paid more and more attention for their unique efficacy in improving depression. In a view from the current study, the positive antidepressant effects of berberine are encouraging. There is a lot of work that needs to be done to accurately elucidate the efficacy and mechanism of berberine in depression. In this review, the relevant literature reports on the treatment of depression and anxiety by berberine are updated, and the potential pharmacological mechanism of berberine in relieving depression has also been discussed.

Sea urchin (Strongylocentrotus intermedius) is an economically important mariculture species in Asia, and its gonads are the only edible part. The efficiency of genetic breeding in sea urchins is hampered due to the inability to distinguish gender by appearance. In this study, we first identified a sex-associated single nucleotide polymorphism (SNP) by combining type IIB endonuclease restriction site-associated DNA sequencing (2b-RAD-seq) and genome survey. Importantly, this SNP is located within spata4, a gene specifically expressed in male. Knocking down of spata4 by RNA interference (RNAi) in male individuals led to the downregulation of other conserved testis differentiation-related genes and germ cell marker genes. We also revealed that sex ratio in this validated culture population of S. intermedius is not 1:1. Moreover, after a 58-day feeding experiment with estradiol, the expression levels of several conserved genes that are related to testis differentiation, ovary differentiation, and estrogen metabolism were dynamically changed. Taken together, our results will contribute toward improving breeding efficiency, developing sex-controlled breeding, and providing a solid base for understanding sex determination mechanisms in sea urchins.

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

Kidney tubule plays a critical role in recovering or secreting solutes, but the detailed morphogenesis remains unclear. Our previous studies have found that grouper tshβ (gtshβ) is also expressed in kidney, however, the distribution significance is still unknown. To understand the gtshβ role and kidney tubule morphogenesis, here, we have generated a transgenic zebrafish line Tg(gtshβ:GFP) with green fluorescent protein driven by the gtshβ promoter. Similar to the endogenous tshβ in zebrafish or in grouper, the gtshβ promoter-driven GFP is expressed in pituitary and kidney, and the developing details of proximal kidney tubule are marked in the transgenic zebrafish line. The gfp initially transcribes at 16 hours post fertilization (hpf) above the dorsal mesentery, and partially co-localizes with pronephric tubular markers slc20a1a and cdh17. Significantly, the GFP specifically localizes in proximal pronephric segments during embryogenesis and resides at kidney duct epithelium in adult fish. To test whether the gtshβ promoter-driven GFP may serve as a readout signal of the tubular development, we have treated the embryos with retinoic acid signaing (RA) reagents, in which exogenous RA addition results in a distal extension of the proximal segments, while RA inhibition induces a weakness and shortness of the proximal segments. Therefore, this transgenic line provides a useful tool for genetic or chemical analysis of kidney tubule.

Objective: To investigate the clinical effect of rituximab combined with CVAD regimen in patients with primary gastrointestinal B-cell lymphoma and serum vascular endothelial growth factor (VEGF) and β2 microglobulin (β2-MG) The impact of the level. Methods: Eighty-four patients with primary gastrointestinal B-cell lymphoma treated from May 2014 to December 2015 were enrolled. Based on the random number table, all the patients were divided into a control group (n=42) and an observation group (n=42). The control group was treated with CVAD. The observation group was treated with rituximab on the basis of the control group. The effect of the patients was evaluated after 3 courses of treatment. The patients were followed up for 3 years after treatment. US RECIST 1.1 was used to evaluate the short-term efficacy on the patients; VEGF, TNF receptor-associated factor 6 (TRAF6) and B-cell lymphoma factor-6 (Bcl-6) levels were measured by enzyme-linked immunosorbent assay;β2-MG level test was implemented to compare the short-term efficacy, biochemical indicators, incidence of toxic side effects and long-term survival rate of the two groups. Results: The short-term efficacy rate of the observation group was 76.19%, which was higher than that of the control group (50.00%) (P<0.05). The levels of VEGF, TRAF6, Bcl-6, and β2-MG were lower in the observation group after 3 courses of treatment than that in the control group (P<0.05); there was no significant difference in the incidence of neutropenia, gastrointestinal reactions, sepsis, infection, infusion-related reactions and cardiovascular events between the observation group and the control group (P>0.05); The 1-year long-term survival rate after treatment was not statistically significant (P>0.05). The long-term survival rate of the observation group was higher than that of the control group at 2 and 3 years after treatment (P<0.05). Conclusion: The combination of rituximab and CVAD in patients with primary gastrointestinal B-cell lymphoma can improve short-term efficacy, lower VEGF and β2-MG levels, and lower incidence of side effects. It can improve the long-term survival rate of patients and is worthy of promotion and application. [ABSTRACT FROM AUTHOR]

Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides. Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively. Significantly, Ecnanos3 3′-untranslated region (UTR) is necessary for PGC specific expression, where a non-canonical “GCACGTTT” sequence is required for miR-430-mediated repression of Ecnanos3 RNA. Furthermore, grouper Dead end (Dnd) can relieve miR-430 repression in PGCs by associating with a 23 bp U-rich region (URR) in Ecnanos3 3′-UTR. The current study revealed the functional association of multiple nanos genes with PGC formation and germ cell development in orange-spotted grouper, and opened up new possibilities for developing biotechnologies through utilizing the associations between Ecnanos3 and PGCs or between Ecnanos2 and GSCs in the hermaphroditic fish. [ABSTRACT FROM AUTHOR]