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Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors. Differential gene expression, enrichment analysis and cellular deconvolution were performed to identify key processes in disease pathology. PPCM and DCM display similar enrichment in metabolic pathways and extracellular matrix remodeling suggesting these are similar processes across end-stage systolic heart failure. Genes involved in golgi vesicles biogenesis and budding were enriched in PPCM left ventricles compared to healthy donors but were not found in DCM. Furthermore, changes in immune cell populations are evident in PPCM but to a lesser extent compared to DCM, where the latter is associated with pronounced pro-inflammatory and cytotoxic T cell activity. This study reveals several pathways that are common to end-stage heart failure but also identifies potential targets of disease that may be unique to PPCM and DCM.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients., Aim: To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls., Methods: We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq)., Results: We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene., Conclusion: Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes., (© 2023. The Author(s).)

Background: Previous study showed that both melatonin supplement and physical exercise intervention could improve sleep quality in children with autism spectrum disorders (ASD) with the increase in endogenous melatonin level. However, none of the studies have directly compared the effectiveness between the two interventions on treating sleep disturbance in children with ASD. Without direct comparison, we do not know which intervention is better. Thus, we designed a study to compare which intervention is more effective to treat sleep disturbance in children with ASD and to examine whether the combination of the two could be the most efficacious. We present a protocol for conducting a randomized controlled trial to compare the effectiveness of physical exercise and melatonin supplement on treating sleep disturbance in children with ASD., Study Design: The proposed study will be a four-group randomised control trial (RCT) design, with equal allocation of participants to the three intervention groups and one control group., Methods: All eligible participants will be randomly allocated to a morning jogging group, a melatonin supplement group, a combination group and a control group. Changes in sleep quality will be monitored through actigraphic assessment and parental sleep logs. Melatonin levels represented by 6-sulfoxymelatonin will be measured from the participants' 24-h and the first morning void urinary samples. All the assessments will be carried out before the intervention (T1), in the mid of the study (5 weeks after the commencement of the study) (T2) and after the 10-week intervention (T3). Level of statistical significance will be set at 5% (i.e. p < .05). The results of this trial will be submitted for publication in peer-reviewed journal., Findings: The findings will provide evidence to determine whether physical exercise or melatonin supplement or the combination of interventions is the most effective to treat sleep disturbance in children with ASD., Competing Interests: The authors declare there is no competing interests with respect to the research, authorship, and/or publication of this article.