Dysregulated Serum Cytokine Production in Pediatric Patients with ß-Thalassemia Major.

ß-Thalassemia major (ß-TM) is an inherited disorder of hemoglobin (Hb) production, which can cause severe anemia. A compromised immune system has been observed in patients with ß-TM, whereas cytokines have a major role in immune modulation. Interleukin-4 (IL-4), IL-8, IL-13 and transforming growth factor-ß (TGF-ß) are critical in initiating pro-inflammatory responses, and the serum levels of those cytokines may be involved in the pathophysiology of ß-thalassemia (ß-thal). To assess this hypothesis, we studied 23 pediatric patients with ß-TM by measuring serum levels of IL-4, IL-8, IL-13 and TGF-ß, as well as evaluating infection frequency per year, total number of transfusions and serum ferritin (SF) levels, together with age-matched healthy controls. We found that patients with ß-thal had higher IL-8, IL-13 and TGF-ß concentrations than normal controls, whereas markedly decreased serum IL-4 level was documented in patients with ß-TM. Serum IL-4 level of ß-thal patients showed a negative significant correlation with infection frequency, total number of transfusions and SF levels. On the contrary, serum levels of IL-8, IL-13 and TGF-ß exerted a positive relationship with those clinical parameters. Taken together, our study implies that dysregulated cytokine profile might contribute to iron overloads and impair immune cell functions, thus serving as useful biomarkers for diagnosis and evaluation of ß-TM in the future. Our study sheds new light on the pathogenesis of ß-TM.

FXR activation prevents liver injury induced by Tripterygium wilfordii preparations.

Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) are the preparations of Tripterygium wilfordii used to treat rheumatoid arthritis (RA) in the clinic, but the hepatotoxicity was reported frequently. This study aimed to determine the potential toxicity mechanism of liver injury induced by the preparations of Tripterygium wilfordii in mice.Here, we performed metabolomic analysis, pathological analysis and biochemical analysis of samples from mice with liver injury induced by TGT and TWT, which revealed that liver injury was associated with bile acid metabolism disorder. Quantitative real-time PCR (QPCR) and western blot indicated that the above changes were accompanied by inhibition of farnesoid X receptor (FXR) signalling.Liver injury from TWT could be alleviated by treatment of the FXR agonist obeticholic acid (OCA) via activation of the FXR to inhibit the c-Jun N-terminal kinase (JNK) pathway and improve bile acid metabolism disorder by activating bile salt export pump (BSEP) and organic solute-transporter-ß (OSTB). The data demonstrate that FXR signalling pathway plays a key role in T. wilfordii-induced liver injury, which could be alleviated by activated FXR.These results indicate that FXR activation by OCA may offer a promising therapeutic opportunity against hepatotoxicity from the preparations of T. wilfordii.

The RopGEF2-ROP7/ROP2 Pathway Activated by phyB Suppresses Red Light-Induced Stomatal Opening.

Circadian rhythm of stomatal aperture is mainly regulated by light/darkness. Blue and red light induce stomatal opening through different mechanisms that are mediated by special receptors. ROP2, a member of Rho GTPase family in Arabidopsis (Arabidopsisthaliana), has been found to negatively regulate light-induced stomatal opening. However, the upstream guanine nucleotide exchange factor (GEF) RopGEFs have not been revealed, and it is unclear which photoreceptor is required for the action of RopGEFs-ROPs. Here, we showed that RopGEF2 acted as a negative regulator in phytochrome B (phyB)-mediated red light-induced stomatal opening. Meanwhile, ROP7, another member of ROP family, acting redundantly with ROP2, was regulated by RopGEF2 in this process. RopGEF2 interacted with ROP7 and ROP2 and enhanced their intrinsic nucleotide exchange rates. Furthermore, the direct interactions between phyB and RopGEF2 were detected in vitro and in plants, and phyB enhanced the GEF activity of RopGEF2 toward both ROP7 and ROP2 under light. In addition, RopGEF4 functioned redundantly with RopGEF2 in red light-induced stomatal opening by activating both ROP7 and ROP2, and RopGEF2/RopGEF4 acted genetically downstream of phyB; however, the GEF activity of RopGEF4 was not directly enhanced by phyB. These results revealed that red light-activated phyB enhances the GEF activities of RopGEF2 and RopGEF4 directly or indirectly, and then activate both ROP7 and ROP2 in guard cells. The negative mechanism triggered by phyB prevents the excessive stomatal opening under red light.

[Overexpression of the truncated fosb isoform (Delta2Deltafosb) increases nodus in CD1 primary osteoblastes].

The recombinant adenoviruses which can overexpress fosb and Delta2Deltafosb proteins were produced. Primary calvarial osteoblasts from new born CD1 mice were infected with those adenoviruses by different proportion of Ad-Delta2Deltafosb and induced by 5 mmol/L beta-glycerophosphate, 50 microg/ml ascorbic acid and 10 nmol/L dexamethasone for 23 days and 29 days, respectively. The results by Alizarin Red Staining showed that the primary osteoblasts overexpressing Delta2Deltafosb protein formed more nodus than the control cells and the nodus in overexpressing Delta2Deltafosb protein osteoblasts were smaller than those in control cells on day 23. Differentiation of the primary osteoblasts overexpressing Delta2Deltafosb protein increased more than that of the control cells on day 29. It is an evidence for the reason that bone density of Delta2Deltafosb transgenic mice was markedly increased throughout the skeleton in new born and mature mice.