The etiology of cancer includes aberrant cellular homeostasis where a compromised RNA regulatory network is a prominent contributing factor. In particular, noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were recently shown to play important roles in the initiation, progression, and metastasis of human cancers. Nonetheless, a mechanistic understanding of noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking. To fill this critical gap in knowledge, we obtained mRNA, miRNA, and lncRNA expression data on patients with LUSC from the updated Cancer Genome Atlas (TCGA) database (2016). We successfully identified 3,366 mRNAs, 79 miRNAs, and 151 lncRNAs as key contributing factors of a high risk of LUSC. Furthermore, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with LUSC and constructed a competitive endogenous RNA (ceRNA) network of LUSC by targeting interrelations with significantly aberrant expression data between miRNA and mRNA or lncRNA. Six ceRNAs (PLAU, miR-31-5p, miR-455-3p, FAM83A-AS1, MIR31HG, and MIR99AHG) significantly correlated with survival (P < 0.05). Finally, real-time quantitative PCR analysis showed that PLAU is significantly upregulated in SK-MES-1 cells compared with 16-BBE-T cells. Taken together, our findings represent new knowledge for a better understanding the ceRNA network in LUSC biology and pave the way to improved diagnosis and prognosis of LUSC.
Theranostic system combined diagnostic and therapeutic modalities is critical for the real-time monitoring of disease-related biomarkers and personalized therapy. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. They have shown attractive properties including painless skin penetration, easy self-administration, prominent therapeutic effects, and good biosafety. Herein, an overview of the microneedles-based diagnosis, therapies, and theranostic systems is given. Four microneedles-based detection methods are concluded based on the sensing mechanism: i) electrochemistry, ii) fluorometric, iii) colorimetric, and iv) Raman methods. Additionally, robust microneedles are suitable for implantable drug delivery. Microneedles-assisted transdermal drug delivery can be primarily classified as passive, active, and responsive drug release, based on the release mechanisms. Microneedles-assisted oral and implantable drug delivery mechanisms are also presented in this review. Furthermore, the key frontier developments in microneedles-mediated theranostic systems as the major selling points are emphasized in this review. These systems are classified into open-loop and closed-loop theranostic systems based on the indirectness and directness of feedback between the transdermal diagnosis and therapy, respectively. Finally, conclusions and future perspectives for next-generation microneedles-mediated theranostic systems are also discussed. Taken together, microneedle-based systems are promising as the new avenue for diagnosis, therapy, and disease-specific closed-loop theranostic applications.
γ-Aminobutyric acid (GABA) is a potentially bioactive ingredient with health-promoting properties that is added to functional foods. Streptococcus thermophilus was selected to produce naturally GABA-enriched fermented milk. This strain can yield a GABA concentration of 2.8 g/L after a 48-h fermentation. In the presence of 1 g/L food-grade casein hydrolysate as a nitrogen source, S. thermophilus yielded GABA concentrations as high as 5.4 g/L or even 8.3 g/L when cocultured with Lactobacillus rhamnosus. In other words, both of these added conditions promoted GABA enrichment. The GABA dose achieved with fermented milk was comparable to the doses of commercially available GABA supplements. Additionally, the in situ use of S. thermophilus to produce GABA-enriched fermented milk was cost effective. The complete genomic sequence of S. thermophilus GABA has been published and will be highly useful to other researchers studying the regulation of genes related to GABA accumulation. In conclusion, the S. thermophilus GABA-producing strain reported herein represents a natural method for the production of fermented milk containing high GABA concentrations.
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