Characterization of Soybean Protein Adhesives Modified by Xanthan Gum

The aim of this study was to provide a basis for the preparation of medical adhesives from soybean protein sources. Soybean protein (SP) adhesives mixed with different concentrations of xanthan gum (XG) were prepared. Their adhesive features were evaluated by physicochemical parameters and an in vitro bone adhesion assay. The results showed that the maximal adhesion strength was achieved in 5% SP adhesive with 0.5% XG addition, which was 2.6-fold higher than the SP alone. The addition of XG significantly increased the hydrogen bond and viscosity, as well as increased the β-sheet content but decreased the α-helix content in the second structure of protein. X-ray diffraction data showed significant interactions between SP molecules and XG. Scanning electron microscopy observations showed that the surface of SP adhesive modified by XG was more viscous and compact, which were favorable for the adhesion between the adhesive and bone. In summary, XG modification caused an increase in the hydrogen bonding and zero-shear viscosity of SP adhesives, leading to a significant increase in the bond strength of SP adhesives onto porcine bones

Combined transcriptome and widely targeted metabolome analysis reveals the potential mechanism of HupA biosynthesis and antioxidant activity in Huperzia serrata

IntroductionHuperzia serrata is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD). However, the biosynthetic pathway and molecular mechanism of HupA in H. serrata are still not well understood.MethodsIntegrated transcriptome and metabolome analysis was performed to reveal the molecular mechanisms related to HupA biosynthesis and antioxidant activity in Huperzia serrata.ResultsHT (in vitro H. serrata thallus) exhibits higher antioxidant activity and lower cytotoxicity than WH (wild H. serrata). Through hierarchical clustering analysis and qRT-PCR verification, 7 important enzyme genes and 13 transcription factors (TFs) related to HupA biosynthesis were detected. Among them, the average |log2FC| value of CYP (Cytochrome P450) and CAO (Copper amine oxidase) was the largest. Metabolomic analysis identified 12 metabolites involved in the HupA biosynthesis and 29 metabolites related to antioxidant activity. KEGG co-enrichment analysis revealed that tropane, piperidine and pyridine alkaloid biosynthesis were involved in the HupA biosynthesis pathway. Furthermore, the phenylpropanoid, phenylalanine, and flavonoid biosynthesis pathway were found to regulate the antioxidant activity of H. serrata. The study also identified seven important genes related to the regulation of antioxidant activity, including PrAO (primary-amine oxidase). Based on the above joint analysis, the biosynthetic pathway of HupA and potential mechanisms of antioxidant in H. serrata was constructed.DiscussionThrough differential transcriptome and metabolome analysis, DEGs and DAMs involved in HupA biosynthesis and antioxidant-related were identified, and the potential metabolic pathway related to HupA biosynthesis and antioxidant in Huperzia serrata were constructed. This study would provide valuable insights into the HupA biosynthesis mechanism and the H. serrata thallus medicinal value

Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC

Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML

Characterization of Soybean Protein Adhesives Modified by Xanthan Gum

The aim of this study was to provide a basis for the preparation of medical adhesives from soybean protein sources. Soybean protein (SP) adhesives mixed with different concentrations of xanthan gum (XG) were prepared. Their adhesive features were evaluated by physicochemical parameters and an in vitro bone adhesion assay. The results showed that the maximal adhesion strength was achieved in 5% SP adhesive with 0.5% XG addition, which was 2.6-fold higher than the SP alone. The addition of XG significantly increased the hydrogen bond and viscosity, as well as increased the β-sheet content but decreased the α-helix content in the second structure of protein. X-ray diffraction data showed significant interactions between SP molecules and XG. Scanning electron microscopy observations showed that the surface of SP adhesive modified by XG was more viscous and compact, which were favorable for the adhesion between the adhesive and bone. In summary, XG modification caused an increase in the hydrogen bonding and zero-shear viscosity of SP adhesives, leading to a significant increase in the bond strength of SP adhesives onto porcine bones

The role and mechanisms of action of microRNAs in cancer drug resistance

Abstract MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19–25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified drug targets, altered cell cycle checkpoints, or increased DNA damage repair, among others. In recent years, many studies have shown that miRNAs are involved in the drug resistance of tumor cells by targeting drug-resistance-related genes or influencing genes related to cell proliferation, cell cycle, and apoptosis. A single miRNA often targets a number of genes, and its regulatory effect is tissue-specific. In this review, we emphasize the miRNAs that are involved in the regulation of drug resistance among different cancers and probe the mechanisms of the deregulated expression of miRNAs. The molecular targets of miRNAs and their underlying signaling pathways are also explored comprehensively. A holistic understanding of the functions of miRNAs in drug resistance will help us develop better strategies to regulate them efficiently and will finally pave the way toward better translation of miRNAs into clinics, developing them into a promising approach in cancer therapy

The Influence of Diabetes Mellitus on Patients Undergoing Primary Total Lower Extremity Arthroplasty: A Systematic Review and Meta-Analysis

Background. Diabetes mellitus (DM) is a common disease that has an adverse impact on most orthopedic surgeries, and its prevalence has gradually increased in recent years. We aim to investigate the influence of DM on comorbidities and complications of patients undergoing primary total lower extremity arthroplasty. Methods. PubMed, Embase, Cochrane Library, Medline, and Web of Science were systematically searched for relevant studies published before December 2019. Demographic data, comorbidities, and postoperative complications after primary total hip arthroplasties (THA) or primary total knee arthroplasties (TKA) were assessed between DM and non-DM patients. Meta-analysis was conducted using Review Manager 5.3, and forest plots were drawn for each variable. Results. A total of 1,560,461 patients (215,916 patients with DM and 1,344,545 patients without DM) from 23 studies were included in this meta-analysis. The incidences of several preoperative comorbidities (hypertension (HTN), kidney disease, cardiac and cerebrovascular disease) were generally higher in patients with DM. Moreover, DM patients had a higher rate of postoperative complications (superficial and deep infection, deep vein thrombosis (DVT), and in-hospital mortality) compared to non-DM patients. Conclusions. DM patients were more likely to suffer from comorbidities and had a higher risk of complications in total lower extremity arthroplasty compared to non-DM patients. It is necessary to identify DM and control hyperglycemia in the perioperative period to prevent postoperative complications in patients with DM

Aggregation of polyethylene glycol polymers suppresses receptor-mediated endocytosis of PEGylated liposomes

ISSN:2040-3364ISSN:2040-337