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MicroRNAs (miRNAs) are important regulators in the process of cardiac hypertrophy and heart failure. Previous studies have shown that miR-199a is upregulated in pressure-overload cardiac hypertrophy and that inhibition of miR-199a attenuates cardiac hypertrophy in vitro. However, the therapeutic role of anti-miR-199a treatment in the cardiac hypertrophy in vivo model is less known. Here, we show an efficient and useful method to treat mouse cardiac hypertrophy and restore cardiac function through injection of adeno-associated virus (AAV)-mediated anti-miR-199a tough decoys (TuDs). RNA-seq transcriptome analysis indicated that genes related to cytoplasmic translation and mitochondrial respiratory chain complex assembly were upregulated in anti-miR-199a-treated recovered hearts. We further validated that PGC-1α is the direct target of miR-199a involved in the therapeutic effect and the regulation of the PGC-1α/ERRα axis and that the downstream pathway of mitochondrial fatty acid oxidation and oxidative phosphorylation constitute the underlying mechanism of the restored mitochondrial structure and function in our anti-miR-199a-treated mice. Our study highlights the important regulatory role of miR-199a in cardiac hypertrophy and the value of the AAV-mediated miRNA delivery system., Graphical Abstract, Previous studies showed that miR-199a is upregulated in pressure-overload cardiac hypertrophy, and inhibition of miR-199a attenuated cardiac hypertrophy in vitro. This study showed an efficient and useful way to treat mice cardiac hypertrophy and restored cardiac function through injection of adeno-associated virus-mediated anti-miR-199a tough decoys targeting the PGC-1α/ERR axis.

Background Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. Methods Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. Findings Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema – patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89. Interpretation Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy., Highlights • The oral microbiota of NPC patients are different to that of healthy persons. • The biodiversity of oral microbiota changed significantly as mucositis progressed during radiotherapy. • Oral microbiota represents a potential strategy for predicting the aggravation of severe mucositis during radiotherapy. Oral or oropharyngeal mucositis is the most common side effect of radiation therapy for head and neck cancers. In this prospective cohort study, we found that changes in an oral microbial community correlated with the progression and aggravation of radiotherapy-induced mucositis in the patients with nasopharyngeal carcinoma; and patients who eventually developed severe mucositis transiently harbored a notably higher proportion of Actinobacillus during a mild phase of mucositis, which may potentially play a role in the aggravation of severe mucosal lesions. Moreover, our findings also showed that microbiota-based strategies can be used for the early prediction of the incidence of severe mucositis during radiotherapy.