Cortisol synergizing with endoplasmic reticulum stress induces regulatory T-cell dysfunction.

The dysfunction of regulatory T cell (Treg) is associated with the pathogenesis of many immune diseases. The regiments used to re-establish Treg's function are currently unsatisfactory and need to be improved. The purpose of this study is to elucidate the synergistic effects of cortisol and endoplasmic reticulum (ER) stress on impairing regulatory T cell functions. In this study, blood samples were collected from patients with food allergy (FA). Immune cells were purified from blood specimens by flow cytometry. A mouse model of FA was established with ovalbumin as a specific antigen. We observed that serum cortisol levels of FA patients were negatively correlated with peripheral Treg counts. Overwhelmed ER stress status was detected in Tregs of FA patients. The antigen-specific immune response induced ER stress in Tregs, which was exacerbated by concurrent cortisol exposure. ER stress mediated the effects of cortisol on impairing the immune suppressive ability of Tregs. The expression of Rnf20 was observed in Tregs upon exposure to cortisol. Rnf20 reduced the expression of Foxp3 and transforming growth factor (TGF)-ß in Tregs. Rnf20 inhibition re-established the immunosuppressive functions of Tregs obtained in patients with FA. The experimental FA in mice was attenuated by inhibition of Rnf20 in Tregs. In summary, specific immune response in synergy with cortisol to induce the expression of Rnf20 in Tregs. Rnf20 reduces the levels of Foxp3 and TGF-ß to impair the immune suppressive function. Inhibition of Rnf20 can restore the immune suppressive ability of Tregs obtained from FA patients.

SIB-IMRT combined with apatinib for unresectable hepatocellular carcinoma in patients with poor response to transarterial chemoembolization.

BACKGROUND: Radiotherapy combined with apatinib exhibits synergistic anti-tumor effect, while the application of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) combined with apatinib in HCC patients is scarce. Hence, this study aimed to explore the treatment response, survival, and safety profile of the SIB-IMRT combined with apatinib in unresectable HCC (uHCC) patients. METHODS: A total of 19 uHCC patients with deficient response to transarterial chemoembolization (TACE), who scheduled for SIB-IMRT combined with apatinib treatment were enrolled. The SIB-IMRT was applied at the following dose: 95% planning target volume (PTV) at 30-50 Gy/2-2.5 Gy/15-20f and 90% Boost of 45-72 Gy/3-4.5 Gy/15-20f at 5 times per week with cone beam computerized tomography validation. During and after radiotherapy, the apatinib was administrated orally with the initial dose of 500 mg per day. RESULTS: The complete response, partial response, stable disease, and progressive disease rates were 31.6%, 36.8%, 21.1% and 10.5%, respectively. Consequently, the objective response rate and disease control rate were 68.4% and 89.5%, respectively. During a median follow-up duration of 9.0 months, the median progression-free survival (PFS) was 6.0 (95% confidential interval (CI): 4.9-7.1) months with 1-year PFS rate of 42.1%; the median overall survival (OS) was not reached with 1-year OS rate of 54.6%. The safety profile was acceptable with the most common adverse events including myelosuppression (42.1%), skin reaction (36.8%), and albuminuria (26.3%). CONCLUSION: SIB-IMRT combined with apatinib exhibits a good efficacy and tolerable safety profile, which could be considered as a potential treatment choice for uHCC patients who have deficient response to TACE.

Biological properties of a novel follicle-stimulating hormone/human chorionic gonadotropin chimeric gonadotropin.

A chimeric recombinant human gonadotropin, termed C3, demonstrates both follitropic and lutropic bioactivities. The alpha-subunit construct for C3 is comprised of the recombinant wild-type human glycoprotein hormone alpha-subunit. The beta-subunit DNA construct for C3 encodes residues 1-145 from human chorionic gonadotropin (hCG)-beta with the exceptions that FSH beta amino acid 88 (D) is substituted for hCG beta amino acid 94 (R) and FSH beta amino acids 95-108 (TVRGLGPSYCSFGE) are substituted for hCG beta amino acids 101-114 (GGPKDHPLTCDDPR). C3 is a potent FSH and LH agonist able to bind and to signal through FSH and LH receptors in vitro. In in vivo bioassays optimized to quantify each type of activity, C3 was found to have lutropin and follitropin potencies at levels similar to those of recombinant human LH and recombinant human FSH, respectively. In immature rats, C3 was sufficient to support the maturation of normal ovarian follicles. Moreover, a significant portion of follicles matured by C3 ruptured in response to an ovulatory hCG stimulus and gave rise to morphologically normal oocytes. Furthermore, a low dose of C3 promoted weight gain in the rodent uterus, suggesting it also supported preparation for implantation without histological evidence of excessive luteinization of the ovary. In summary, the biological properties of C3 indicate that its chimeric nature has resulted in a fully functional, dual-acting human gonadotropin.

[Suspension culture of protocorm-like bodies from the endangered medicinal plant Dendrobium huoshanenese].

OBJECTIVE: To investigate the characteristics of growth, and water-soluble polysaccharide and total alkaloid accumulation in protocom-like bodies (PLBs) of Dendrobium huoshanenese in liquid culture system. METHOD: PLBs were suspended in liquid medium and growth kinetics was analyzed. Water-soluble polysaccharide and total alkaloid content in PLBs were determined by colorimetry. RESULT: PLBs were induced from stem explants of D. huoshanenese regenerants cultured on MS medium supplemented with NAA or NAA and KT at different concentrations. Basal MS medium was suitable for propagation of PLBs. When PLBs were suspended in liquid medium, mumax was 0.044.d-1, t(d) was 15.8 d and the optimum growth time was 4 weeks. Water-soluble polysaccharide and total alkaloid contents in PLBs were 3.75% and 0.0261%, respectively. CONCLUSION: PLBs in liquid culture system show a potential for rapid growth and high metabolite synthesis, which provides possibility for exploiting resources of D. huoshanenese by large scale culture of PLBs.