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Biomedical subjects

Qiuying Chen

Publications and source records attributed to Qiuying Chen.

3 recordsLinked to original sources

Insights into the mechanism of enhanced tetramethylpyrazine production in dehulled adlay fermented by Bacillus subtilis BJ3-2.

Tetramethylpyrazine (TTMP) is a vital bioactive alkaloid and characteristic flavor compound in fermented foods. Our previous study found that fermentation of adlay by Bacillus subtilis BJ3-2 efficiently accumulates TTMP, whereas the underlying high-yield mechanism remains unclear. This study investigated the fermentation characteristics, gene transcription and protein expression of B. subtilis BJ3-2 in dehulled adlay (BDA) and soybean (BSB), respectively, and elucidated the mechanism responsible for high-yield TTMP production. The results showed that glutamate, leucine and phenylalanine were major free amino acids in BDA. The TTMP yield in BDA at 48 h (6.11 mg/g dry weight) was 360-fold higher than that in BSB. Transcriptomic and proteomic analysis demonstrated that compared with the soybean substrate, dehulled adlay substrate significantly up-regulated the expression of alsSD and ilvBH genes and their encoding proteins in B. subtilis BJ3-2, which were involved in C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, and valine, leucine and isoleucine biosynthesis. Meanwhile, acetoin degradation was inhibited by down-regulating acetoin dehydrogenase complex (acoABCL) in citrate cycle, glycolysis/gluconeogenesis and carbon metabolism. Additionally, nitrogen metabolism pathway was transcriptionally enhanced to guarantee sufficient ammonium supply. Notably, protein-protein interaction and molecular docking analyses revealed that acetohydroxyacid synthase (ilvBH) interacted tightly with α-acetolactate decarboxylase (alsD), potentially forming a metabolic channel for acetoin synthesis. In conclusion, the efficient synthesis of TTMP in BDA was primarily attributed to the high synthesis and low degradation of acetoin, and the moderate synthesis of ammonium/ammonia. This study provided a theoretical basis for the targeted and efficient biosynthesis of TTMP.

Bacillus subtilis

Ampyrone is a direct agonist of human tyrosinase and a potential therapeutic for hypopigmentation disorders.

Significant loss of pigmentation can increase visual disability, skin cancer risk, and psychosocial stress. Tyrosinase (TYR) catalyzes the first and rate-limiting step of melanin synthesis. Inhibitors of TYR are well established and are currently used in clinical settings; however, there is a dearth of direct activators of TYR. Here, using a human TYR construct, we developed high-throughput screening methods, in cell confirmatory assays employing 13C-tyrosine tracing, and computational analysis techniques, and identified ampyrone (4-aminoantipyrine) as a TYR activator. Ampyrone increased the in vitro catalytic activity of the human recombinant intramelanosomal domain of TYR (hTYR) and its hypomorphic variant, Pro406Leu (P406L), a cause of oculocutaneous albinism type 1B (OCA1B). Moreover, ampyrone induced melanin synthesis in both WT and OCA1B human melanocytes, mouse OCA2 melanocytes, as well as 3-dimensional (3D) human skin cultures. Computational studies provided additional insight into the effects of direct TYR agonists on enzyme activity. Our results identify ampyrone as a lead candidate for TYR activation, potentially supporting the development of therapies for patients with genetic and acquired diseases of hypopigmentation.

Humans

Exogenous BMI1 expression aggravates oral squamous cell carcinomas in tongue epithelia.

Oral squamous cell carcinoma (OSCC) is characterized by aggressiveness and a poor prognosis, in part because most patients are diagnosed during the later stages of the disease. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), part of polycomb repressive complex 1 (PRC1), is a key transcription factor overexpressed in OSCC. Although increased BMI1 has been linked to tumor formation in mouse models of the disease, the molecular mechanisms have not been elucidated. Here we used a transgenic mouse line (KrTB) that selectively overexpresses BMI1 in the tongue basal epithelial stem cells (SCs) to delineate BMI1 actions during oral tumorigenesis. By tumor pathological classification after 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis we detected more severe tumors in mice with ectopic BMI1 expression. Genome-wide transcriptomics indicated that mRNAs associated with human OSCC, including SOX9, HIF1A, MMP9, INHBB, and MYOF, were further increased by ectopic BMI1 expression in murine tongue epithelia. mRNAs encoding multiple metabolic targets, such as SLC2A1 (GLUT1), PKM, LDHA, and HK2, were also increased upon BMI1 overexpression in 4-NQO-treated tongue epithelia. Furthermore, we detected BMI1, SOX9, and GLUT1 proteins in the infiltrating cells of invasion fronts identified by markers of invasive SCCs. Finally, metabolomic data show that BMI1 overexpression in tongue epithelia promotes glycolysis during 4-NQO-induced carcinogenesis. Thus, our data demonstrate that BMI1 causes OSCC cells to alter cell metabolism, as changes in many of these transcripts are linked to increased glycolysis and metabolic reprograming that occurs during carcinogenesis.

Animals