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Nonalcoholic fatty liver disease (NAFLD) has become the most important chronic liver disease in the world, but there is still no approved drug for clinical practice. Due to the heterogeneity of NAFLD itself, although drug therapy is being developed, the response rate seems to remain low. In order to meet the needs of clinical trial design and provide accurate information for drug developers, relevant scholars have proposed to change the name of NAFLD to metabolic associated fatty liver disease This article summarizes the origin of NAFLD heterogeneity and the background of NAFLD renaming, so as to provide new ideas for accelerating the development of new therapies.
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Objective To investigate association of vitamin D receptor (VDR) polymorphisms with susceptibility to psoriasis vulgaris and clinical response to calcipotriol in patients with psoriasis vulgaris.Methods A total of 110 patients with psoriasis vulgaris and 183 healthy controls were enrolled into this study,and they were all of Han nationality from Hainan province.Ligase detection reaction (LDR) was conducted to determine the genotypes of VDR gene polymorphisms rs2228570,rs731236,rs1544410 and rs7975232.Single nucleotide polymorphism (SNP)-based association analysis in genotypic and allelic models,and haplotype-based association analysis were then performed.Then,75 patients with psoriasis area and severity index (PASI) scores less than 10 were topically treated with calcipotriol ointment alone.After 6-week treatment,the efficacy of calcipotriol ointment was evaluated,and the correlation between the efficacy and individual genotypes was analyzed.Results The frequency of A allele of rs7975232 in the psoriasis group and control group was 39.09％ and 27.05％ respectively,and the risk of developing psoriasis in rs7975232 A allele carriers was significantly higher than that in non-carriers (OR =1.731,95％ CI:1.213-2.471,P ＜ 0.05).Additionally,the risk of developing psoriasis in individuals with AA genotype (OR =2.404,95％ CI:1.085-5.328,P ＜ 0.05),as well as in individuals with AC genotype (OR =2.143,95％ CI:1.283-3.579,P ＜ 0.05),was significantly higher than that in patients with CC genotype.CTGA haplotype carriers (rs2228570,rs731236,rs1544410,rs7975232,respectively) had significantly higher risk of developing psoriasis compared with non-carriers (OR =1.907,95％ CI:1.132-3.214,P ＜ 0.05).Among 72 patients with mild-to-moderate psoriasis whose PASI scores were less than 10,patients with CC genotype of rs7975232 showed better response to calcipotriol ointment compared with those with AC genotype (OR =3.798,95％ CI:1.061-13.590,P ＜ 0.05) and those with AA genotype (OR =9.667,95％CI:1.556-60.040,P ＜ 0.05).Conclusion VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in patients with psoriasis individuals.
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Objective To investigate the relationship of serum IL-6 levels with cognitive dysfunction among patients with obstructive sleep apnoea syndrome (OSAS).Methods Patients diagnosed with OSAS by polysomnography (PSG) received assessment of cognitive function with Montreal Congnitive Assessment (MoCA).According to the result of MoCA assessment,patients were divided into two groups,without cognitive dysfunction group (n =47) and with cognitive dysfunction group (n =55);30 health volunteers were used as control.Serum IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA) in three groups;according to the apnea hypopnea index (AHI),OSAS patients with cognitive dysfunction were divided into three groups,light group (n =15),moderate group (n =16),and severe group (n =24),and differences in MoCA scores and serum IL-6 levels were analyzed among three groups.The correlation of serum IL-6 levels and MoCA scores were analyzed in OSAS patients with cognitive dysfunction.Results Serum levels of IL-6 in OSAS patients with cognitive dysfunction [(197.3 ± 72.58) pg/ ml] were significantly increased than those without cognitive dysfunction [(155 ± 39.3)pg/ml] as well as health control [(87.39 ±33.44)pg/ml] (P ＜0.01).For OSAS patients with cognitive dysfunction,MoCA scores were decreased and the level of serum IL-6 was increased among patients with poor AHI grade,with statistically significant difference.Pearson correlation analysis showed serum IL-6 levels were significantly negatively correlated with MoCA scores among OSAS patients with cognitive dysfunction (r =-0.65,P ＜ 0.01).Conclusions Serum levels of IL-6 in OSAS patients with cognitive dysfunction were significandy increased and correlated with the cognitive dysfunction.OSAS patients with cognitive dysfunction experiencing sever AHI grade have more serious cognitive dysfunction and the higher serum levels of IL-6.
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Calcineurin (CaN) serves as a key enzyme in human immune regulation. The most important target of this enzyme is the transcription factors of nuclear factors of activated T cells (NFATc). The discovery of the immunosuppressive function of CaN inhibitors (CNIs),ciclosporin A (CsA) and tacrolimus (FK506),has helped overcome the immune rejection of organ transplantion and changed organ transplantion fundamentally. Both of these drugs are still widely used in clinical and basic research,but their therapeutic effects are limited by their serious side effects,including renal tox?icity and neurotoxicity. Therefore,the development of new CNIs with higher specificity and fewer side effects in the clinic is a focus of research. In this paper,the newly discovered and synthesized CNIs in recent decades,including the CsA and FK506 derivatives,direct inhibitors of CaN,as well as the inhibitors that specifically interfere with CaN-NFATc interaction,were summarized.
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G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility.