Epidemiologic studies have shown that the treatment of diabetics with metformin reduced the risk of cancer-related mortality. Here, we investigated the chemopreventive effects of metformin on dimethylhydrazine (DMH)-induced colorectal carcinogenesis in diabetic SD rats following metformin treatment and the effect on Warburg effect involved in this process. Diabetic rat models were induced with high-fat feeding in combination with a low dose of Streptozotocin (STZ) and then induce colorectal cancer with a low dose of DMH. The formation of colorectal Aberrant crypt foci (ACF) and the incidence, number and size of the tumor were measured. The proliferation indices of colonic tissues were determined through Proliferating cell nuclear antigen (PCNA) immunostaining. Then detect the expression of PK and IDH in colonic tissues using immunohistochemistry and Western blot. The enzyme activities of HK and PDH in colonic tissues were measured. The growth and expression of PK and IDH and activity of HK and PDH in cell lines LoVo and HT-29 were measured after metformin treatment. The results showed that metformin treatment significantly inhibited the formation of ACF and tumors. The proliferation index of colonic tissues was significantly decreased following metformin treatment. In addition, metformin inhibited cell growth and decreased the imbalance in the expression of the enzymes involved in glycolysis and the TCA cycle. These findings suggested that metformin might produce a synergistic colon cancer-preventative effect in diabetic patients through the regulation of the enzymes expression involved in glucose metabolism.

Na+/K+-ATPase (NKA) belongs to the P-type ATPase family, whose members are located in the cell membrane and are distributed in diverse tissues and cells. The main function of the NKA is to regulate osmotic pressure. To better understand the role of NKA in osmoregulation, we first cloned and characterized the full-length cDNAs of NKA α subunit and β subunit from Pacific abalone Haliotis discus hannai in the current study. The predicted protein sequence of the NKA α subunit, as the catalytic subunit, was well conserved. In contrast, the protein sequence of the β subunit had low similarity with those of other species. Phylogenetic analysis revealed that both the α and β subunits of the NKA protein of Pacific abalone were clustered with those of the Gastropoda. Then, the relationship between salinity changes and the NKA was investigated. Sudden salinity changes (with low-salinity seawater (LSW) or high-salinity seawater (HSW)) led to clear changes in ion concentration (Na+ and K+) in hemolymph; however, the relative stability of ion concentrations in tissue revealed that Pacific abalone has a strong osmotic pressure regulation ability when faced with these salinity changes. Meanwhile, the expression and activity of the NKA was significantly decreased (in LSW group) or increased (in HSW group) during the ion concentration re-establishing stages, which was consistent with the coordinated regulation of ion concentration in hemolymph. Moreover, a positive correlation between cyclic adenosine monophosphate (cAMP) concentrations and NKA mRNA expression (NKA activity) was observed in mantle and gill. Therefore, the sudden salinity changes may affect NKA transcription activation, translation and enzyme activity via a cAMP-mediated pathway.

the two subspecies of atlantic bay scallop (Argopecten irradians), A. i. irradians and A. i. concentricus, are economically important aquacultural species in northern and southern China. Here, we performed the whole-genome sequencing, assembly, and gene annotation and produced draft genomes for both subspecies. In total, 253.17 and 272.97 gigabases (Gb) of raw reads were generated from Illumina Hiseq and PacBio platforms for A. i. irradians and A. i. concentricus, respectively. Draft genomes of 835.7 Mb and 874.82 Mb were assembled for the two subspecies, accounting for 83.9% and 89.79% of the estimated sizes of their corresponding genomes, respectively. The contig N50 and scaffold N50 were 78.54 kb and 1.53 Mb for the A. i. irradians genome, and those for the A. i. concentricus genome were 63.73 kb and 1.25 Mb. Moreover, 26,777 and 25,979 protein-coding genes were predicted for A. i. irradians and A. i. concentricus, respectively. these valuable genome assemblies lay a solid foundation for future theoretical studies and provide guidance for practical scallop breeding.

The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.

Background: Aquaporins (AQPs), as members of the major intrinsic protein (MIP) superfamily, facilitated the permeation of water and other solutes and are involved in multiple biological processes. AQP family exists in almost all living organisms and is highly diversified in vertebrates in both classification and function due to genome wide duplication. While some AQP orthologs have been lost in higher vertebrates through evolution. Result: Genome-wide comparative analyses of the AQP family between allotetraploid frog Xenopus laevis (Xla) and diploid frog Xenopus tropicalis (Xtr), based on the genome assemblies, revealed that the number of AQPs in Xla genome nearly doubled that in Xtr (32 vs. 19). Synteny analysis indicated that the distribution of the retained AQPs in Xla subgenomes (17 in Xla. L, the longer homeolog of Xla genome and 15 in Xla. S, the shorter homeolog of Xla genome) were highly symmetrical when compared with that in Xtr genome. Remarkably, two members in Xla. L and four members in Xla. S were lost through evolution. Blast analysis revealed that the lost AQPs in Xla are pseudogenized via either the deletion of some exons or some single nucleotide insertions or deletions that lead the reading frame shift. Additionally, comparative genomic analyses suggested that the orthologs of AQPs that with one copy absence in Xla are also prone to be lost in higher vertebrates. Conclusion: This study revealed that polyploidization and subsequent pseudogenization and deletion in Xla genome promote the evolution of AQP family in higher vertebrates. Besides, our results would also contribute to understanding the evolution of AQP family.

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Background The diversified aquaporin (AQP) family that was derived from gene duplication and subsequent functional differentiation play critical roles in multiple physiological processes and in adaptation to the dynamic environments during the evolutionary process. Oysters are a group of bivalve fauna in Mollusca that were widely distributed around the world and show extraordinary adaptation to harsh environments. However, knowledge is lacking with the diversity and evolution of the AQP family in oysters, even in molluscs. Results Here, we performed a comprehensive analysis of the AQP family in three geographical isolated oyster species that are native to different environments. Genome distribution and phylogenetic analysis revealed that the expansion of the AQP family in oysters were attributed to tandem duplication. Synteny analysis indicated that large-scale inversions lead to the independent duplication or deletion of the AQPs after speciation. As a consequence, these independent duplication events contributed to the diversification of the AQP family in different oysters. Pore pattern analysis suggested that the duplicated AQPs in oysters were highly diversified in inner surface profiles, implying the subsequent functional differentiation. The comparison conducted based on the transcriptome data demonstrated that the functional differentiated AQP family members in oysters may play critical roles in maintaining the balance between the stationary homeostasis and dynamic environments. Conclusions Our observation provides evidence for the correlation between the duplicated and functional differentiated AQP family and the adaptation to stationary life under dynamic environments in oysters. Additionally, it also broadens our knowledge of the evolution of AQP family in molluscs.