Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

This paper reports the comparison of determination methods for extra virgin olive oil (EVOO) adulteration with two kinds of oils, refined olive oil (ROO) and soybean oil by ¹⁹FNMR, ¹H NMR and chemical titration. The determination of adulteration of EVOO with ROO by ¹⁹F NMR was comparable to the conventional method. The contents of oleic, linoleic and linolenic acids of different oil samples can be determined by both ¹H NMR and GC-MS. The results obtained from the two methods showed little differences. The adulteration of EVOO with soybean oil is detected by ¹H NMR, although the limit of detection of the adulteration level is not less than 4.5%. The research demonstrates that ¹⁹F NMR can be a fast and convenient method to detect EVOO if it is adulterated with ROO and ¹H NMR can be a fast and convenient method to detect EVOO if it is adulterated with seed oils.

A novel antioxidant, butylated caffeic acid (BCA) was rationally designed by adding a tert-butyl group to caffeic acid, which was synthesized at a high yield (36.2%) from 2-methoxy-4-methylphenol by a four-step reaction including Friedel-Crafts alkylation, bromine oxidation, ether bond hydrolysis and Knoevenagel condensation. Its antioxidant capacity was much stronger than common commercial antioxidant tert-butyl hydroquinone (TBHQ) and its mother compound, caffeic acid, in both rancimat and deep frying tests. When investigated via the DPPH method, the antioxidant capacity of BCA was almost equal to TBHQ, but lower than caffeic acid. BCA could be a potentially strong antioxidant, especially for food processing at high temperatures such as deep frying and baking.

Background: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. Methods and results: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. Conclusions: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.

Hyperoxia-induced bronchopulmonary dysplasia (BPD) is a major cause of lung injury in premature infants. Epigenetics, particularly DNA (hydroxy)methylation, has been identified as a crucial regulator of BPD pathogenesis. This study aimed to reveal key regulators and pathogenic genes involved in hyperoxia-induced BPD via DNA (hydroxy)methylation and transcriptional analysis. Multi-omics analyses including RNA-seq, reduced representation bisulfite sequencing (RRBS), and oxidative RRBS (oxRRBS) were conducted on lung tissues from hyperoxia-induced rat BPD model. Differentially methylated and hydroxymethylated regions (DMRs and DhMRs) were further detected by targeted bisulfite sequencing (TBS) and oxidative TBS (oxTBS). Differentially expressed genes (DEGs) were finally verified in hyperoxia-exposed lung tissues by qPCR, western blotting, and immunohistochemistry. Our integrated analysis identified 2058 DEGs, 62,123 DMRs, and 33,212 DhMRs in hyperoxia-induced BPD. Among them, eighteen candidate genes with altered expression patterns were revealed to be involved in BPD-related pathways. Notably, ten candidate genes, including Cxcl6, Gpr39, Hs6st2, Htatip2, Apln, Calca, Hist1h1t, Lgals3, Rarres1, and Rasl2-9, exhibited significant upregulation with both hypo-DNA methylation and hyper-DNA hydroxymethylation levels. Conversely, eight candidate genes, containing Krt76, Spon2, Abcc6, Egfl7, Gpbar1, Myh6, Tgfbi, and Tmem100, displayed pronounced downregulation associated with both hyper-DNA methylation and hypo-DNA hydroxymethylation levels. Most importantly, the upregulation of Apln and Calca was further validated in hyperoxia-induced BPD, which was characterized by reduced DNA methylation and increased DNA hydroxymethylation levels at their promoter regions. This study reveals that hyperoxia triggers decreased DNA methylation together with increased DNA hydroxymethylation at promoter regions of Apln and Calca, promoting their gene expression and contributing to BPD pathogenesis.