Therapeutic effect and metabolic fingerprinting of triple-negative breast cancer cells following exposure to a novel pH-responsive, gambogic acid-loaded micelle.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and lacks effective therapeutic targets. The use of gambogic acid (GA), a class of active ingredients in traditional Chinese medicine with anti-tumour potential, is limited in tumour therapy owing to its drawbacks and unclear organ toxicity. In this study, we used the pH-responsive amphiphilic block copolymer, PEOz-PCL, to create nanodrugs for GA delivery to MDA-MB-231 cells. The pH-responsive GA-loaded micelles were prepared through nanoprecipitation with a more homogeneous size. The average particle size was 42.29 ± 1.74 nm, and the zeta potential value was 9.88 ± 0.17 mV. The encapsulation rate was 85.06%, and the drug loading rate was 10.63%. The process was reproducible, and sustained release reached 80% in 96 h at acid pH 5.0. Furthermore, cellular tests using CCK-8, TUNEL, and flow cytometry revealed that pH-responsive GA-loaded micelles killed MDA-MB-231 cells more effectively and had much higher activity and targeting compared with free drugs. Metabolomic analysis of the changes in differential metabolites revealed that pH-responsive GA-loaded micelles may inhibit TNBC cells by causing amino acid anabolism, nucleotide metabolism, and glucose metabolism, as well as by affecting their energy sources. The study outcomes will help understand the mechanism of action and the therapeutic efficacy of pH-responsive GA-loaded micellesin vivo.

Characterization of the oral microbiome and gut microbiome of dental caries and extrinsic black stain in preschool children.

Introduction: A lower prevalence of dental caries (hereafter termed "caries") has been observed in children with dental extrinsic black stain (EBS). Methods: We investigated the epidemiologic characterization of EBS and explored the possible role of the oral microbiome (OM) and gut microbiome (GM) in EBS formation and caries prevention. In an epidemiologic survey, 2,675 children aged 3-6 years were included. Thirty-eight of these children (7 children had both caries and EBS, 10 had EBS only, 11 had caries only, and 10 were healthy children) were recruited for 16S rRNA sequencing and collection of samples of supragingival plaque and feces. Collected plaque samples were divided into four groups: BCP (EBS+, caries+), BP (EBS+, caries-), CP (EBS-, caries+), and P (EBS-, caries-). Fecal samples were also divided into four groups: BCF (EBS+, caries+), BF (EBS+, caries-), CF (EBS-, caries+), and F (EBS-, caries-). Results: EBS was observed in 12.10% of this population. Children with EBS had a significantly reduced prevalence of caries and a lower mean value of decayed-missing-filled teeth (dmft; p < 0.01). According to analyses of dental plaque, the P group had the most complex microbiome. The BCP group exhibited greater operational taxonomic unit (OTU) richness but a reduced evenness compared with the BP group, and the CP group showed greater OTU richness than the BP group. At the genus level, higher abundance of Actinomyces and Cardiobacterium species was observed in the BCP group. Higher abundance of Lautropia and Pesudopropionibacteriumin species was observed in the BP group compared with P and CP groups, respectively (p < 0.05). Veillonella species were significantly more common in P and CP groups than in BP groups, whereas Porphyromonas and Fusobacterium species were more common in the CP group (p < 0.05). With regard to the GM, the CF group exhibited greater OTU diversity than the BF group. The GM in the BCF group exhibited the most complex relationships across all fecal groups. GM groups could be distinguished by various unique biomarkers, such as Escherichia and Shigella species in the BCF group, Agathobacter and Ruminococcus species in the CF group, Lactobacillus species in the BF group, and Roseburia species in the F group. Our results suggest that EBS is a possible protective factor against early-childhood caries. Dental plaque and the GM may be relevant to EBS in primary dentition.

Knockdown of kinesin family member 2C restricts cell proliferation and induces cell cycle arrest in gastric cancer.

Kinesin family member 2C (KIF2C) was reported to act as a vital player in several human cancers. However, the exact function of KIF2C in gastric cancer (GC) is poorly understood. In the present study, the potential role of KIF2C was studied in gastric cancer by bioinformatics analysis and proliferation assay. KIF2C expression was detected using reverse transcription-quantitative polymerase chain reaction and western blot. Our data showed that the expression of KIF2C was increased in different tumor tissues, including GC. KIF2C was overexpressed in GC tissues and might be used as a diagnostic and prognostic biomarker for GC. KIF2C expression was correlated with immune infiltration and the levels of cell cycle-related genes in GC. Moreover, silencing of KIF2C can cause cell cycle arrest, and inhibit the proliferative ability of GC cells. Thus, our studies revealed that KIF2C levels might serve as a promising biomarker for diagnosis and prediction of prognosis of GC, and targeting KIF2C might be an effective therapeutic strategy for GC.

Hydrothermal Synthesis of MnO2 Microspheres and Their Degradation of Toluene.

Various urchin-like MnO2 materials were obtained with a facile hydrothermal method through controlling the Mn precursor, reaction time, and reaction temperature. The property of MnO2 materials was characterized by scanning electron microscopy, X-ray diffraction, and H2 temperature-programmed reduction. The results showed that the Mn precursor could significantly impact the morphology of as-prepared MnO2. When the precursor was Mn(CH3COO)2·4H2O, the MnO2 morphology consisted of tennis-like microspheres assembled by nanorods. While the precursor was MnCl2·4H2O, the sample morphology was a chestnut shell, and the samples were sea urchin microspheres, as the precursor was MnSO4·H2O. At the same time, the morphology of MnO2 was affected by hydrothermal time and temperature. The nanoneedles on the microsphere surface gradually lengthened with increasing hydrothermal time and hydrothermal temperature, until nanowires were formed. MnO2 crystallinity was also influenced by hydrothermal temperature. It was γ-MnO2 as the temperature was 50 and 80 °C while evolved to be α-MnO2 and ß-MnO2 when the temperature increased to 140 °C. As MnO2 (MnO2-1 h, MnO2-2 h, MnO2-4 h, and MnO2-6 h) was prepared to degrade toluene, all the samples could completely catalyze toluene at the temperature of 225 °C. However, the MnO2-4 h showed the best catalytic effect at a lower temperature.

A pan-cancer analysis of the expression of STAT family genes in tumors and their relationship to the tumor microenvironment.

Background: The signal transducer and activator of transcription (STAT) protein family, a group of seven members (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6), has been widely used to investigate numerous biological functions including cell proliferation, differentiation, apoptosis, and immune regulation. However, not much is known about the role of the STAT family genes in pan-cancer. Methods: Tumor Immune Estimation Resource (TIMER), Sangerbox, cBioPortal, GSCALite, Xena Shiny, GeneMANIA, Gene Expression Profiling Interactive Analysis (GEPIA), and Metascape were used to analyze the relationship between STAT gene expression, clinical outcome, gene variation, methylation status, pathway activity, tumor immune infiltration, and microenvironment in different cancer types and screened drugs that could potentially influence STATs. Results: The Cancer Genome Atlas (TCGA) pan-cancer data showed that most STAT family genes were extensively changed in most tumors compared to the adjacent normal tissues. We also found that STAT gene expression could be used to predict patient survival in various cancers. The STAT gene family formed a network of interaction networks that was associated with several pathways. By mining the of Genomics Drug Sensitivity in Cancer (GDSC) database, we discovered a number of potential drugs that might target STAT regulators. Importantly, the close correlation between STATs and immunocell infiltration suggested the important role of dysregulation of STATs in tumor immune escape. Finally, the relation between STAT gene expression and the tumor microenvironment (TME) indicated that the higher expression of STAT regulators, the higher the degree of tumor stem cells. Conclusion: Considering these genomic alterations and clinical features of STAT family members across cancer types, it will be possible to change the relationship between STATs and tumorigenesis. It was beneficial to treat cancer by targeting these STAT regulators.

MiR-185 acts as a tumor suppressor by targeting AKT1 in non-small cell lung cancer cells.

Increasing evidence has shown that microRNAs play critical roles in the initiation and progression of non-small cell lung cancer (NSCLC). miR-185 is deregulated in various cancers, whereas its functional mechanism in NSCLC is still unclear. Here, we confirmed that the expression of miR-185 was significantly down-regulated in NSCLC tissues and cell lines. miR-185 over-expression caused significant suppression of in vitro cell proliferation, migration and invasion, and in vivo tumor growth. We subsequently identified that AKT1 was a target gene of miR-185. Re-expression of AKT1 could partially rescue the inhibitory effects of miR-185 on the capacity of NSCLC cell proliferation and motility. Collectively, we conclude that miR-185 has a critical function by blocking AKT1 in NSCLC cells, and it may be a novel therapeutic agent for miRNA based NSCLC therapy.