A recently evolved BAHD acetyltransferase,responsible for bitter soyasaponin A production,is indispensable for soybean seed germination

Soyasaponins are major small molecules that accumulate in soybean (Glycine max) seeds. Among them, type-A soyasaponins, fully acetylated at the terminal sugar of their C22 sugar chain, are responsible for the bitter taste of soybean-derived foods. However, the molecular basis for the acetylation of type-A soyasaponins remains unclear. Here, we identify and characterize GmSSAcT1, encoding a BADH-type soyasaponin acetyltransferase that catalyzes three or four consecutive acetylations on type-A soyasaponins in vitro and in planta. Phylogenetic analysis and biochemical assays suggest that GmSSAcT1 likely evolved from acyltransferases present in leguminous plants involved in isoflavonoid acylation. Loss-of-function mutants of GmSSAcT1 exhibited impaired seed germination, which attribute to the excessive accumulation of null-acetylated type-A soyasaponins. We conclude that GmSSAcT1 not only functions as a detoxification gene for high accumulation of type-A soyasaponins in soybean seeds but is also a promising target for breeding new soybean varieties with lower bitter soyasaponin content.     

Neonatal Proinflammatory Stress and Expression of Neuroinflammation-Associated Genes in the Rat Hippocampus

Biochemistry (Moscow) - Differential effect of the neonatal proinflammatory stress (NPS) on the development of neuroinflammation in the hippocampus and induction of the depressive-like behavior in...     

The emerging role of small non-coding RNA in renal cell carcinoma

Noncoding RNAs are transcribed in the most regions of the human genome, divided into small noncoding RNAs (less than 200 nt) and long noncoding RNAs (more than 200 nt) according to their size. Compelling evidences suggest that small noncoding RNAs play critical roles in tumorigenesis and tumor progression, especially in renal cell carcinoma. MiRNA, the most famous small noncoding RNA, has been comprehensively explored for its fundamental role in cancer. And several miRNA-based therapeutic strategies have been applied to several ongoing clinical trials. However, piRNAs and tsRNAs, have not received as much research attention, because of several technological limitations. Nevertheless, some studies have revealed the presence of aberration of piRNAs and tsRNAs in renal cell carcinoma, highlighting a potentially novel mechanism for tumor onset and progression. In this review, we provide an overview of three classes of small noncoding RNA: miRNAs, piRNAs and tsRNAs, that have been reported dysregulation in renal cell carcinoma and have the potential for advancing diagnosis, prognosis and therapeutic applications of this disease.     

Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil

5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzyme thymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, we report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. We found that 10 μM 5-FU and 10 μM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-κB (NF-κB), and this observation was confirmed by silencing TS and inactivating NF-κB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-κB activation, whereas inactivation of NF-κB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-κB and regulates the activation of NF-κB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FU may improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials.