Effects of voluntary slow breathing on heart rate and heart rate variability: A systematic review and a meta-analysis.

Voluntary slow breathing (VSB) is used as a prevention technique to support physical and mental health, given it is suggested to influence the parasympathetic nervous system (PNS). However, to date, no comprehensive quantitative review exists to support or refute this claim. We address this through a systematic review and meta-analysis of the effects of VSB on heart rate variability (HRV). Specifically, we focus on HRV parameters indexing PNS activity regulating cardiac functioning, referred to as vagally-mediated (vm)HRV: (1) during the breathing session (i.e., DURING), (2) immediately after one training session (i.e., IM-AFTER1), as well as (3) after a multi-session intervention (i.e., AFTER-INT). From the 1842 selected abstracts, 223 studies were suitable for inclusion (172 DURING, 16 IM-AFTER1, and 49 AFTER-INT). Results indicate increases in vmHRV with VSB, DURING, IM-AFTER1, and AFTER-INT. Given the involvement of the PNS in a large range of health-related outcomes and conditions, VSB exercises could be advised as a low-tech and low-cost technique to use in prevention and adjunct treatment purposes, with few adverse effects expected.

Baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins fine-tune TNF-induced nuclear factor κB and c-Jun N-terminal kinase signalling in mouse pancreatic beta cells.

AIMS/HYPOTHESIS: For beta cells, contact with TNF-α triggers signalling cascades that converge on pathways important for cell survival and inflammation, specifically nuclear factor κB (NF-κB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase pathways. Here, we investigated the function of baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins in regulating TNF signalling cascades. METHODS: TNF regulation of Birc genes was studied by mRNA expression and promoter analysis. Birc gene control of cell signalling was studied in beta cell lines, and in islets from Birc2(-/-) and Birc3(-/-) mice, and from Birc3(-/-) Birc2Δ beta cell mice that selectively lack Birc2 and Birc3 (double knockout [DKO]). Islet function was tested by intraperitoneal glucose tolerance test and transplantation. RESULTS: TNF-α selectively induced Birc3 in beta cells, which in turn was sufficient to drive and potentiate NF-κB reporter activity. Conversely, Birc3(-/-) islets exhibited delayed TNF-α-induced IκBα degradation with reduced expression of Ccl2 and Cxcl10. DKO islets showed a further delay in IκBα degradation kinetics. Surprisingly, DKO islets exhibited stimulus-independent and TNF-dependent hyperexpression of TNF target genes A20 (also known as Tnfaip3), Icam1, Ccl2 and Cxcl10. DKO islets showed hyperphosphorylation of the JNK-substrate, c-Jun, while a JNK-antagonist prevented increases of Icam1, Ccl2 and Cxcl10 expression. Proteosome blockade of MIN6 cells phenocopied DKO islets. DKO islets showed more rapid loss of glucose homeostasis when challenged with the inflammatory insult of transplantation. CONCLUSIONS/INTERPRETATION: BIRC3 provides a feed-forward loop, which, with BIRC2, is required to moderate the normal speed of NF-κB activation. Paradoxically, BIRC2 and BIRC3 act as a molecular brake to rein in activation of the JNK signalling pathway. Thus BIRC2 and BIRC3 fine-tune NF-κB and JNK signalling to ensure transcriptional responses are appropriately matched to extracellular inputs. This control is critical for the beta cell's stress response.