BackgroundCorynebacterium crenatum SYPA 5 is the industrial strain for l-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and l-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the l-arginine biosynthesis in C. crenatum SYPA 5.ResultsC. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of l-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L l-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key l-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9–3.0 times compared with the parent strain.ConclusionsAccumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time l-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular l-arginine and intracellular PHB simultaneously. All of these have a potential biotechnological application as a strategy for high-yield l-arginine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0414-x) contains supplementary material, which is available to authorized users.

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response ( IL1A, IL2 , and IL6R ) and cell proliferation ( CCND1, PPARG , and EGFR ) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.

Bone tissue is a common metastatic site of lung cancer, and bone metastasis is characterized by abnormal differentiation and malfunction of osteoclast, and the roles of exosomes derived from lung cancer have attracted much attention.In our study, we found that the level of HOTAIR expression in A549 and H1299 exosomes was higher than those of normal lung fibrocytes. Overexpression of HOTAIR in A549 and H1299 exosomes promoted osteoclast differentiation. Furthermore, A549-Exos and H1299-Exos targeted bone tissues, and bone formation was significantly inhibited in vivo. Mechanistically, exosomal lncRNA HOTAIR promoted bone resorption by targeting TGF-β/PTHrP/ RANKL pathway.

The aim of current study was to exhume the potential targets and molecular mechanisms of oxyresveratrol, a structurally re-constructed resveratrol, for treating liver cancer through bioinformatics investigation and experimentative validation. To start with, the network pharmacology approach and molecular docking technology were used to uncover all candidate targets of oxyresveratrol to treat liver cancer, accompanied with identified anti-liver cancer targets including estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR). In addition, more pharmacological mechanisms of oxyresveratrol against liver cancer were revealed in details. In experimental verification, the clinical samples of liver cancer showed elevated ESR1, EGFR mRNA expressions. The in-vitro data indicated that intracellular contents of ESR1, EGFR mRNAs in oxyresveratrol-treated liver cancer cells were reduced. Taken together, the bioinformatics and validated findings have highlighted detailed pharmacological targets and molecular mechanisms of oxyresveratrol for treating liver cancer. Following with experimental verification, the identified genes of ESR1, EGFR may function as potential screening anti-liver cancer markers.

BackgroundHeart failure (HF) and diabetes mellitus (DM) are life-threatening diseases. However, existing clinical drugs to treat HF complicated with DM are relatively limited. In this study, we performed a viable bioinformatics strategy combining network pharmacology and molecular docking to identify potential anti-HF and -DM targets and therapeutic mechanisms of calycosin, a functional phytoestrogen.MethodsWeb-based databases were used to collect candidate genes/targets of calycosin and HF/DM and then identify the hub bio-targets of calycosin against HF/DM. Using the online-available database, all functional processes and signaling pathways of calycosin against HF/DM were screened and identified before further visualization.ResultsAll potential bio-targets of calycosin and HF/DM were collected, and 20 hub targets of calycosin against HF/DM were identified. Interestingly, molecular docking findings indicated that mitogen-activated protein kinase-1 (MAPK1), β-arrestin 1 (ARRB1), and homologue-1 (ABL1) may be potent pharmacological targets of calycosin against HF/DM. In addition, all primary molecular functions of calycosin against HF/DM were identified, including regulating protein binding, ubiquitination, and the metabolic process. Furthermore, the top molecular pathways of calycosin against HF/DM were revealed, including cardiomyocyte and chemokine signaling pathways.ConclusionOur bioinformatics analysis uncovered the network targets and therapeutic mechanisms of calycosin against HF/DM. For the first time, the current in silico findings revealed that the identified hub targets may be used to screen and treat HF/DM.