Recent Advances in Natural Products with Anti-Leukemia and Anti-Lymphoma Activities.

Leukemia and lymphoma are the most common blood cancers, which pose a critical threat to the health of adults and children. The total incidence and mortality rates of both are approximately 6% globally. Compared with the expensive cost of CAR T cell therapy, natural products from animals, plants and microorganisms have the characteristics of wide-range sources and costeffectiveness in the treatment of cancer. Moreover, the drug resistance that emerged in leukemia and lymphoma treatments shows an urgent need for new drugs. However, in addition to the natural products that have been marketed in the treatment of leukemia and lymphoma, there have been a large number of studies on natural products that fight blood cancer in recent years. This review summarized the recent studies on natural compounds with anti-lymphoma and anti-leukemia activities, hoping to provide novel weapons into the drug development arsenal.

Identification of GnRH-like peptide and its potential signaling pathway involved in the oocyte meiotic maturation in the Chinese mitten crab, Eriocheir sinensis.

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproductive regulation in vertebrates. However, GnRH was rarely isolated and its function remains poorly characterized in invertebrates. The existence of GnRH in ecdysozoa has been controversial for a long. Here, we isolated and identified two GnRH-like peptides from brain tissues in Eriocheir sinensis. Immunolocalization showed that the presence of EsGnRH-like peptide in brain, ovary and hepatopancreas. Synthetic EsGnRH-like peptides can induce germinal vesicle breakdown (GVBD) of oocyte. Similar to vertebrates, ovarian transcriptomic analysis revealed a GnRH signaling pathway in the crab, in which most genes exhibited dramatically high expression at GVBD. RNAi knockdown of EsGnRHR suppressed the expression of most genes in the pathway. Co-transfection of the expression plasmid for EsGnRHR with reporter plasmid bearing CRE-luc or SRE-luc response element into 293T cells showed that EsGnRHR transduces its signal via cAMP and Ca2+ signaling transduction pathways. In vitro incubation of the crab oocyte with EsGnRH-like peptide confirmed the cAMP-PKA cascade and Ca2+ mobilization signaling cascade but lack of a PKC cascade. Our data present the first direct evidence of the existence of GnRH-like peptides in the crab and demonstrated its conserved role in the oocyte meiotic maturation as a primitive neurohormone.

Integration of RNAi and RNA-seq uncovers the regulation mechanism of DDX20 on vitellogenin expression in Scylla paramamosain.

Vitellogenesis in crustaceans is controlled by several steroid hormones. In humans, the expression of SF-1, a gene that regulates gonadal development and the synthesis of steroid hormones, is affected by DDX20. However, how the homologous gene FTZ-F1 is regulated by DDX20 and its association with vitellogenesis remains unknown in the mud crab Scylla paramamosain. In this study, SpDDX20 and SpFTZ-F1 were identified in the transcriptome of mature ovarian tissue from the mud crab. qRT-PCR results revealed that the expression levels of SpFTZ-F1 and SpVTG in the ovaries of crab in the experimental group injected with dsDDX20 (EO) were significantly higher (P < 0.05) than those in the negative control group injected with dsEGFP (NO) and the blank control group injected with SPSS (BO). The differentially expressed genes (DEGs) identified by comparative transcriptome analysis of the EO group and NO group were enriched into five pathways related to ovarian steroidogenesis. The expression of CYP17, CYP3A4, CYP1A1 and 3ß-HSD were up-regulated in pathways related to steroid hormone production and biosynthesis. The expression of the INSR, IRS and PI3K genes in the insulin signaling pathway were significantly increased (P < 0.05). The expression level of the TGF-ß gene was up-regulated (P < 0.05) in the transforming growth factor pathway, whereas the expression level of the Smad2 gene was down-regulated (P < 0.05). The expression of GnRHR, GS, AC and PKA genes in the gonadotropin-releasing hormone signaling pathway were up-regulated. Our data provide a foundation for investigating the relationship between DDX20 and FTZ-F1 in the regulation of vitellogenin expression in S. paramamosain.

Differentially expressed lncRNAs involved in immune responses of Haliotis diversicolor and H. discus hannai challenged with Vibrio parahaemolyticus.

Although many studies have shown that lncRNA, a non-coding RNA with a length of more than 200 bases, is involved in various biological functions, including the immune process, stress process, and cell development process. However, the function of lncRNA in abalone, especially in immunity, has been rarely studied. H. discus hannai and H. diversicolor are two main aquaculture abalone, and their growth is easily affected by the main pathogen Vibrio parahaemolyticus. Through rigorous screening procedures for transcripts in this study, we found that lncRNAs were 34,240, 23,022 in Haliotis diversicolor and H. discus hannai injected with V. parahaemolyticus, respectively. We also identified the unique and common lncRNAs and mRNAs of two abalone species for the first time; the shared lncRNAs and mRNAs in Haliotis diversicolor and H. discus hannai were 2352 and 13,165, respectively. Then gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed target genes of common and unique lncRNAs has shown that common lncRNAs could be widely involved in the biological processes of stress and cell development in both abalone species. In contrast, unique lncRNAs are linked to the Toll-like receptor, NF-kappaB signaling pathway of H. diversicolor, and pattern recognition receptors and lectins immune-related pathways of H. discus hannai. The co-expression network shows that some immune-related genes, such as INFK1, INFK2, CASP2, CASP8, IRAK1, lectin C, were closely related to lncRNAs. Further, we identified the targeted relationship between some immune-related genes and lncRNAs by qRT-PCR, through which we showed that the expression trend between targeted genes, such as INFK1 and Lnc7057, lectin C and Lnc6943, Lnc5637, and PLCG1 and Lnc1692, were consistent. In general, our results showed that lncRNA expression was induced in the two species of abalone after being infected with V. parahaemolyticus, and lncRNA was involved in the immune response of abalone by targeting coding genes.

Characterization of two myostatin genes in pufferfish Takifugu bimaculatus: sequence, genomic structure, and expression.

Myostatin (MSTN) is a negative regulator of muscle growth, which restrains the proliferation and differentiation of myoblasts. To understand the role of two mstn genes of Takifugu bimaculatus, the full-length cDNAs of 1131 bp Tbmstn1 and 1,080 bp Tbmstn2 were obtained from the T. bimaculatus' genomic database, which encodes 376 and 359 amino acids, respectively. The results of qRT-PCR showed that Tbmstn1 was expressed in the eye, kidney, spleen, skeletal muscle, gill, and brain, and the expression level in the skeletal muscle was extremely significantly higher than in other examined tissues. Tbmstn2 was expressed in the skin, skeletal muscle, gill, and brain, and had the highest expression in the skeletal muscle, followed by expression in the brain. Meanwhile, in different stages of embryonic development, the expression of Tbmstn1 started from the gastrula stage. Its expression in the eye-pigment formation stage and hatching stage was significantly higher than that in other stages. The Tbmstn2 was expressed in all examined embryonic stages with different levels, and the highest expression was detected in the eye-pigment formation stage. These results suggested that Tbmstn1 and Tbmstn2 may involve in the development of skeletal muscle, and Tbmstn2 may be related to the formation of nervous system.

Genome-wide identification and expression profile of the sox gene family in different tissues and during embryogenesis in the Pacific white shrimp (Litopenaeus vannamei).

Sox transcription factors play essential roles in a variety of critical physiological processes. Still, members of the sox gene family have not yet been genome-wide identified in shrimps. In this study, a total of five members of the sox gene family were identified from the genome of Pacific white shrimp Litopenaeus vannamei and classified into three subgroups based on the conserved HMG-box domain. Among them, three belong to the SoxB subgroup (one in B1 and two in B2), one in the SoxC subgroup, and one in the SoxE subgroup. The five sox genes had different sex-biased expression in some tissues. Sox21, soxB1, and sox14 had a higher expression in ovary than in testis. In comparison, sox4 had a male-biased specific expression in the gonad, hepatopancreas, gill, and eyestalk. There was no difference in soxE gene expression between testis and ovary. During embryonic development, the expression level of three sox genes (soxB1, sox21, and soxE) was higher in gastrulation stage compared to previous stages, declined in limb bud stage and then increased in intramembrane nauplius stage; the expression of sox4 was detected in blastula stage and continued to increase in the following two stages and then surged in intramembrane nauplius stage; the highest expression of sox14 was in the fertilized egg stage, and the expression level decreased with the development of the embryo. These results suggest that the shrimp sox gene family may be involved in gametogenesis, tridermogenesis, and neurogenesis.

Effects of validamycin in controlling Fusarium head blight caused by Fusarium graminearum: Inhibition of DON biosynthesis and induction of host resistance.

Validamycin, known to interfere with fungal energy metabolism by inhibiting trehalase, has been extensively used to control plant diseases caused by Rhizoctonia spp. However, the effect of validamycin on controlling Fusarium graminearum has not been previously reported. In this study, when applied to F. graminearum in vitro, validamycin inhibited the synthesis of deoxynivalenol (DON), which is a mycotoxin and virulence factor, by decreasing trehalase activity and the production of glucose and pyruvate, which are precursors of DON biosynthesis. Because FgNTH encodes the main trehalase in F. graminearum, these effects were nullified in the FgNTH deletion mutant ΔFgNTH but restored in the complemented strain ΔFgNTHC. In addition, validamycin also increased the expression of pathogenesis-related genes (PRs) PR1, PR2, and PR5 in wheat, inducing resistance responses of wheat against F. graminearum. Therefore, validamycin exhibits dual efficacies on controlling Fusarium head blight (FHB) caused by F. graminearum: inhibition of DON biosynthesis and induction of host resistance. In addition, field trials further confirmed that validamycin increased FHB control and reduced DON contamination in grain. Control of FHB and DON contamination by validamycin increased when the antibiotic was applied with the triazole fungicide metconazole. Overall, this study is a successful case from foundational research to applied research, providing useful information for wheat protection programs against toxigenic fungi responsible for FHB and the consequent mycotoxin accumulation in grains.