Additional file 1 of Elevated RIF1 participates in the epigenetic abnormalities of zygotes by regulating histone modifications on MuERV-L in obese mice

Additional file 1: Table S1. Quantitative real-time PCR primers used in this study

Additional file 1 of Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury

Additional file1: Figure S1. Specific number and proportion of mice that died/survived (included in the assay) after modeling between the different groups, as well as the chi-square test between the groups

Discovery of Novel, Potent, and Selective Small-Molecule Menin–Mixed Lineage Leukemia Interaction Inhibitors through Attempting Introduction of Hydrophilic Groups

Introduction of the N,N-dimethylaminoethoxy group to pyrido[3,2-d]pyrimidine led to the discovery of menin–mixed lineage leukemia (MLL) interaction inhibitor C20. C20 showed strong binding affinity to menin protein and achieved sub-micromolar potency in cell growth inhibition. C20 had good selectivity for the inhibition of the interaction between menin and MLL in the kinase profile evaluation. Pharmacokinetic studies demonstrated that C20 possessed good stability and low clearance rate in liver microsomes and acceptable bioavailability in rats. Subsequent oral administration of C20 showed potent antitumor activity in the MV4;11 subcutaneous xenograft models of MLL-rearranged leukemia. The docking study showed that C20 bound highly with menin, and the N,N-dimethylaminoethoxy group occupied the F9 pocket of menin. This study proved that introducing a hydrophilic group into the F9 pocket of menin would be a new strategy for the design of menin–MLL interaction inhibitors with potent binding affinity and improved physical properties

Discovery of Novel, Potent, and Selective Small-Molecule Menin–Mixed Lineage Leukemia Interaction Inhibitors through Attempting Introduction of Hydrophilic Groups

Introduction of the N,N-dimethylaminoethoxy group to pyrido[3,2-d]pyrimidine led to the discovery of menin–mixed lineage leukemia (MLL) interaction inhibitor C20. C20 showed strong binding affinity to menin protein and achieved sub-micromolar potency in cell growth inhibition. C20 had good selectivity for the inhibition of the interaction between menin and MLL in the kinase profile evaluation. Pharmacokinetic studies demonstrated that C20 possessed good stability and low clearance rate in liver microsomes and acceptable bioavailability in rats. Subsequent oral administration of C20 showed potent antitumor activity in the MV4;11 subcutaneous xenograft models of MLL-rearranged leukemia. The docking study showed that C20 bound highly with menin, and the N,N-dimethylaminoethoxy group occupied the F9 pocket of menin. This study proved that introducing a hydrophilic group into the F9 pocket of menin would be a new strategy for the design of menin–MLL interaction inhibitors with potent binding affinity and improved physical properties

Validation of the differential expression of six known miRNAs by qPCR analysis.

<p>The miRNA expression level was normalized to that of U6 snRNA. “*” represents P value <0.05, “**” represents P value <0.01, and “***” represents P value <0.001. All experiments were repeated with 3 replicates.</p

The 62 novel miRNAs expressed in the human decidua and menstrual endometrium.

<p>Candidates with sequence overlap with known miRNAs (but having a distinct mature miRNA sequence: isomiRs) and sequence alignments of novel miRNA candidates with known miRNAs of other species are shown.</p

Hypoxia-Responsive Stereocomplex Polymeric Micelles with Improved Drug Loading Inhibit Breast Cancer Metastasis in an Orthotopic Murine Model

Tumor metastasis is a leading cause of breast cancer-related death. Taxane-loaded polymeric formulations, such as Genexol PM and Nanoxel M using poly­(ethylene glycol)-poly­(d,l-lactide) (PEG-PLA) micelles as drug carriers, have been approved for the treatment of metastatic breast cancer. Unfortunately, the physical instability of PEG-PLA micelles, leading to poor drug loading, premature drug leakage, and consequently limited drug delivery to tumors, largely hinders their therapeutic outcome. Inspired by the enantiomeric nature of PLA, this work developed stereocomplex PEG-PLA micelles through stereoselective interactions of enantiomeric PLA, which are further incorporated with a hypoxia-responsive moiety used as a hypoxia-cleavable linker of PEG and PLA, to maximize therapeutic outcomes. The results showed that the obtained micelles had high structural stability, showing improved drug loading for effective drug delivery to tumors as well as other tissues. Especially, they were capable of sensitively responding to the hypoxic tumor environment for drug release, reversing hypoxia-induced drug resistance and hypoxia-promoted cell migration for enhanced bioavailability under hypoxia. In vivo results further showed that the micelles, especially at a high dose, inhibited the growth of the primary tumor and improved tumor pathological conditions, consequently remarkably inhibiting its metastasis to the lungs and liver, while not causing any systemic toxicity. Hypoxia-responsive stereocomplex micelles thus emerge as a reliable drug delivery system to treat breast cancer metastasis

MicroRNA Profiles in Spontaneous Decidualized Menstrual Endometrium and Early Pregnancy Decidua with Successfully Implanted Embryos - Fig 3

<p>(a) Let-7f-5p was predicted to bind to a site on the <i>IGF2BP-1</i> mRNA. (b) Let-7g-5p was predicted to bind to a site on the <i>IGF-2R</i> mRNA.</p

Kyoto Encyclopedia of Genes and Genomes analysis indicating the number of miRNA-targeted genes and the various associated pathways.

<p>Horizontal axis indicates the annotated signaling pathways identified, and the vertical axis indicates the number of genes in each pathway to which miRNAs were predicted to bind.</p

IGF2BP-1 expression in vitro after overexpression or knockdown of let-7f-5p.

<p>(a) Overexpression of let-7f-5p in HEK293T and hESCs cells. Cells were cultured and incubated with hsa-let-7f-5p mimic or negative control. Levels of let-7f-5p were determined using qPCR. (b) Knockdown of let-7f miRNA by transfection with hsa-let-7f-5p inhibitor. Cells were cultured and incubated with hsa-let-7f-5p inhibitor or negative control. Levels of let-7f-5p were determined using qPCR. (c-d) Expression of <i>IGF2BP-1</i> mRNA, as determined using qPCR analysis. Experiments were replicated three times, and error bars represent standard error. **P<0.01, ***P<0.001.</p