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Farnesoid X receptor (FXR) is expressed in human and rodent placentas. Nevertheless, its function remains obscure. This study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal death and intrauterine growth restriction. All pregnant mice except controls were i.p. injected with LPS (100 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to GD17. As expected, placental FXR signaling was activated by OCA. OCA pretreatment protected against LPS-induced fetal death. In addition, OCA pretreatment alleviated LPS-induced reduction of fetal weight and crown-rump length. Additional experiments showed that OCA inhibited LPS-evoked TNF-α in maternal serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced upregulation of placental proinflammatory genes including Tnf-α, Il-1β, IL-6, Il-12, Mip-2, Kc, and Mcp-1. By contrast, OCA elevated anti-inflammatory cytokine IL-10 in maternal serum, amniotic fluid, and placenta. Further analysis showed that OCA blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth zone. These results provide a mechanistic explanation for placental FXR-mediated anti-inflammatory activity. Overall, this study provides evidence for roles of FXR as an important regulator of placental inflammation.

Background: The traditional Chinese theory of acupuncture emphasizes that the intensity of acupuncture must reach a threshold to generate de qi, which is necessary to achieve the best therapeutic effect. De qi is an internal compound sensation of soreness, tingling, fullness, aching, cool, warmth and heaviness, and a radiating sensation at and around the acupoints. However, the notion that de qi must be achieved for maximum benefit has not been confirmed by modern scientific evidence. Methods: We performed a prospective multicentre randomized controlled trial involving patients with Bell palsy. Patients were randomly assigned to the de qi ( n = 167) or control ( n = 171) group. Both groups received acupuncture: in the de qi group, the needles were manipulated manually until de qi was reached, whereas in the control group, the needles were inserted without any manipulation. All patients received prednisone as a basic treatment. The primary outcome was facial nerve function at month 6. We also assessed disability and quality of life 6 months after randomization. Results: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR] 4.16, 95% confidence interval [CI] 2.23–7.78), better disability assessment (differences of least squares means 9.80, 95% CI 6.29–13.30) and better quality of life (differences of least squares means 29.86, 95% CI 22.33–37.38). Logistic regression analysis showed a positive effect of the de qi score on facial-nerve function (adjusted OR 1.07, 95% CI 1.04–1.09). Interpretation: Among patients with Bell palsy, acupuncture with strong stimulation that elicited de qi had a greater therapeutic effect, and stronger intensity of de qi was associated with the better therapeutic effects. Trial registration: Clinicaltrials.gov no. NCT00685789.

The association between maternal cadmium (Cd) exposure during pregnancy and the increased risk of fetal growth restriction (FGR) remains controversial. The present study evaluated the association between maternal serum Cd level and risk of small for gestational age (SGA) infants in a Chinese population. The present study analyzed a subsample of the C-ABCS cohort that recruited 3254 eligible mother-and-singleton-offspring pairs. Maternal serum Cd level during pregnancy was measured by graphite furnace atomic absorption spectrometry. The rate and odds ratio (OR) for SGA infant were calculated. The rate for SGA infant was 10.6% among subjects with H-Cd (≥1.06 μg/L), significantly higher than 7.5% among subjects with L-Cd (OR was 1.45 (95% CI: 1.11, 1.90; P = 0.007) among subjects with H-Cd. Adjusted OR for SGA infants was 1.43 (95% CI: 1.09, 1.88; P = 0.007) among subjects with H-Cd. Taken together, we observe the fact that maternal Cd exposure at middle gestational stage, elevates the risk of SGA in contrast to early gestational stage. The present results might be interesting and worth more discussing, and guarantee to further studies.

To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the microenvironment of axonal regeneration after spinal cord injury (SCI).Forty-five SD rats were randomly divided into 3 equal groups: SCI group undergoing SCI by hemisection technique and peritoneal injection of dimethyl sulfoxide (DMSO) solution 30 min after the SCI, SCI + olomoucine (SCI + Olo) group undergoing SCI by hemisection technique and peritoneal injection of olomoucine solution 30 min after the SCI, and sham operation group undergoing sham operation and peritoneal injection of DMSO solution 30 min after the operation. Three days after the operation the injured spinal cord segments of 5 rats from each group were taken out. Western blotting was used to detect the expression of the cell cycle related proteins, cyclin A, cyclin B, cyclin E, and proliferating cell nuclear antigen (PCNA). Immunofluorescence (IF) staining was used to detect the expression of glial fibrillary acidic protein (GFAP), growth associated protein-43 (GAP-43) and chondroitin sulphate proteoglycan (CSPG). Four weeks after the operation specimens of the injured spinal cord segment 15 mm in length were taken out from 5 rats in each group to undergo histological examination. The locomotion function of the hindlimbs was determined by modified Gale combined behavioral scoring (SBS) 1 day and 1, 2, 4, 6, and 8 weeks after the operation.Western blotting 3 days after the operation showed that the expressions of cyclin A, cyclin B, cyclin E, and PCNA were very weak in the sham operation group, were significantly increased in the SCI group, and were significantly down-regulated in the SCI + Olo group compared with those of the SCI group. IF staining showed that the number of astrocytes was small and the expressions of GFAP, CSPG, and GAP-43 were weak in the sham operation group; in the SCI group the astrocytic proliferation and glial scar was obvious, and the expressions of GFAP, CSPG, and GAP-43 were significantly increased compared with those of the sham operation group (all P0.05); and the astrocytic proliferation was significantly weaker and no obvious glial scar could be seen, and the expressions of GFAP and CSPG were weaker in the SCI + Olo group in comparison with the SCI group, however, the GAP-43 expression of the sham operation group was significantly increased compared with that of the sham operation group (P0.05). The hindlimbs of the SCI + Olo group and sham operation group were paralyzed without significant difference in the CBS values between these 2 groups, however, two weeks after the operation, the locomotion function scores at different time points of the SCI + Olo group were all significantly improved in comparison with that of the SCI group (all P0.05).Olomoucine promotes the recovery of the locomotion function of the paralyzed hindlimbs, probably through microenvironmental improvement of axonal regeneration by inhibiting the glial scar formation and CSPG secretion as well as upregulating the GAP-43 expression.