GPR15-C10ORF99 functional pairing initiates colonic Treg homing in amniotes.

Regulatory T lymphocyte (Treg) homing reactions mediated by G protein-coupled receptor (GPCR)-ligand interactions play a central role in maintaining intestinal immune homeostasis by restraining inappropriate immune responses in the gastrointestinal tract. However, the origin of Treg homing to the colon remains mysterious. Here, we report that the C10ORF99 peptide (also known as CPR15L and AP57), a cognate ligand of GPR15 that controls Treg homing to the colon, originates from a duplication of the flanking CDHR1 gene and is functionally paired with GPR15 in amniotes. Evolutionary analysis and experimental data indicate that the GPR15-C10ORF99 pair is functionally conserved to mediate colonic Treg homing in amniotes and their expression patterns are positively correlated with herbivore diet in the colon. With the first herbivorous diet in early amniotes, a new biological process (herbivorous diet short-chain fatty acid-C10ORF99/GPR15-induced Treg homing colon immune homeostasis) emerged, and we propose an evolutionary model whereby GPR15-C10ORF99 functional pairing has initiated the first colonic Treg homing reaction in amniotes. Our findings also highlight that GPCR-ligand pairing leads to physiological adaptation during vertebrate evolution.

Acupressure for labor pain management: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy/effectiveness of acupressure as an adjunct to standard procedures during labor and delivery, compared with standard procedures with/without sham acupressure, in randomized controlled trials (RCTs). METHODS: Ten main databases were searched from their inception until 31 January 2018. Two reviewers independently extracted data concerning the effects of acupressure on pain intensity, labor duration, mode of delivery, use of medications and adverse events. A meta-analysis of these measures was performed using RevMan 5.3. Pooled standardized mean differences (SMDs) or odds ratios (ORs) for the above outcomes were estimated with a fixed or random effects model, according to the heterogeneity. RESULTS: A total of 13 RCTs including 1586 enrolled patients met the eligibility criteria. Acupressure plus standard procedures (ASP) for labor management significantly reduced pain sensation, compared with sham acupressure plus standard procedures (SASP) and standard procedures (SP) alone. The analgesic effect of acupressure was immediate and persisted for at least 60 min (all p < 0.01). Compared with the untreated control groups, the acupressure group had a shorter duration of labor, especially the first stage of labor (SMD = -0.76, 95% confidence interval (CI) = -1.10 to -0.43; p < 0.001; I2 = 74%) and second stage of labor (SMD = -0.37, 95% CI = -0.59 to -0.18; p < 0.001; I2 = 0%). Data suggesting that acupressure reduced the Cesarean section rate was inconclusive. The use of pharmacologic agents (oxytocin and analgesics) did not differ between the ASP, SASP and SP groups. No adverse events were reported in this limited number of studies. CONCLUSION: Moderate evidence indicates that acupressure may have promising effects on labor pain and duration. However, high-quality trials to verify these findings are warranted.