While the metabolic changes in cancer tissues were first observed by Warburg Otto almost a century ago, altered metabolism has recently returned as a focus of cancer research. 5'-Methylthioadenosine (MTA) is a naturally occurring sulfur-containing nucleoside found in numerous species. While MTA was first isolated several decades ago, a lack of sensitive and specific analytical methodologies designed for its direct quantification has hampered the study of its physiological and pathophysiological features. Many studies indicate that MTA suppresses tumors by inhibiting tumor cell proliferation, invasion, and the induction of apoptosis while controlling the inflammatory micro-environments of tumor tissue. In this review, we assessed the effects of MTA and of related materials on the growth and functions of normal and malignant cells.

Extracellular protein disulfide isomerase (PDI) is a promising target for thrombotic-related diseases. Four potent PDI inhibitors with unprecedented chemical architectures, piericones A–D (1–4), were isolated from Pieris japonica. Their structures were elucidated by spectroscopic data analysis, chemical methods, quantum 13C nuclear magnetic resonance DP4+ and electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Piericones A (1) and B (2) were nanomolar noncompetitive PDI inhibitors possessing an unprecedented 3,6,10,15-tetraoxatetracyclo[7.6.0.04,9.01,12]pentadecane motif with nine contiguous stereogenic centers. Their biosynthetic pathways were proposed to include a key intermolecular aldol reaction and an intramolecular 1,2-migration reaction. Piericone A (1) significantly inhibited in vitro platelet aggregation and fibrin formation and in vivo thrombus formation via the inhibition of extracellular PDI without increasing the bleeding risk. The molecular docking and dynamics simulation of 1 and 2 provided a novel structure basis to develop PDI inhibitors as potent antithrombotics.

Shikonin has been testified to wield the anti-tumor action in multiple cancers. But, the clout of Shikonin for gastric cancer (GC) is still inconclusive. The contemplation of this research undertook to disclose the impacts of Shikonin on GC progress meanwhile to uncover the conceivable mechanism. NCI-N87 cells were disposed by Shikonin at diverse concentration points. The trials of CCK-8, colony formation, flow cytometry and Transwell assays were executed for detecting the functions of Shikonin in NCI-N87 cells. The impacts of miR-195 on Shikonin-regulated PI3K/AKT pathway were estimated via western blot. The in vivo trial was detected by xenografts model assay. We found that Shikonin suppressed cell survival and triggered apoptosis in NCI-N87 cells. Additionally, Shikonin restrained cell migration, invasion and down-regulated MMP2, RhoA, ROCK1 and Vimentin expression in NCI-N87 cells. Furthermore, Shikonin notably inhibited PI3K/AKT signal pathway, but the restraining functions were repealed by miR-195 inhibition in NCI-N87 cells. The in vivo trial results revealed that Shikonin determinately impeded tumor formation. In conclusion, these results demonstrated that Shikonin prohibited NCI-N87 cells proliferation, migration, invasion, and accelerated apoptosis by inactivation of PI3K/AKT pathway. The findings maybe provide a fresh opinion for healing GC.

Sperm-mediated gene transfer (SMGT) has been long heralded as a faster and cheaper alternative to more commonly used methods of producing transgenic animals. In this study, the capra semen ejaculates were pooled together and then incubated in vitro with DIG-labeled DNA. The binding and internalizing rates were observed by the in situ hybridization methods. We also compared the standard sperm parameters and the efficiencies of interaction with exogenous DNA of 60 individuals to select donor bucks for SMGT. It was showed that labeled exogenous DNA was detected in different localizations in spermatozoa but genuine DNA uptake, in contrast to mere binding, seems to be limited to the postacrosomal region. The removal of seminal plasma increased significantly (P < 0.01) the capability in picking up exogenous DNA. Use of frozen-thawed semen (without cryoprotectant agents) and Triton X-100 treatment also increased significantly (P < 0.01) the DNA-binding capacity, but reduced the sperm viability. The binding rates (the proportion of labeled-DNA positive spermatozoa to all the spermatozoa counted) of 60 buck individuals were in the range of 3.08-73.39%, and the internalizing rates (the proportion of DNaseI-treated labeled-DNA positive spermatozoa to all the spermatozoa counted) were 4.83-70.00%. About 8.34% (5/60) bucks showed high binding, but low internalizing ability. Chi-square test showed that there was significant difference among the breeds (x(2) = 26.515, P < 0.01). Eight individual bucks that demonstrated high DNA uptake were selected for SMGT. It was demonstrated that the goat spermatozoa was capable of spontaneous uptake of exogenous DNA. Seminal fluid inhibits DNA uptake and that membrane disruption increases DNA binding but greatly diminishes uptake.

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