Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc. METHODS: Bleomycin-induced mice and SSc dermal fibroblasts were treated with Yiqihuoxue decoction; NIH-3T3 fibroblasts were exposed to exogenous TGF-β1, and then cultured with or without Yiqihuoxue decoction. Luciferase reporter gene assay was used to determine the activity of Smad binding element (SBE). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA levels of extracellular matrix (ECM) genes. The protein levels of type I collagen, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected by western blotting. Student’s t-tests were used to determine the significance of the results. RESULTS: Bleomycin-induced mice, SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts showed higher levels of ECM gene transcriptions and collagen production. In addition, the phosphorylation level of Smad3 and activity of SBE were significantly increased after exogenous TGF-β1 induction. Whereas, Yiqihuoxue treatment could obviously attenuate fibrosis in bleomycin-induced mice, down regulate ECM gene expressions and collagen production in SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts. Furthermore, the aberrantly high phosphorylation level of Smad3 and activity of SBE in the TGF-β1-induced NIH/3T3 fibroblasts were also dramatically decreased by Yiqihuoxue treatment. CONCLUSIONS: Yiqihuoxue treatment could effectively reduce collagen production via down-regulating the phosphorylation of Smad3 and then the activity of SBE, which are involved in the TGF-β pathway and constitutively activated in the progression of SSc

Polydopamine-clay functionalized Calotropis gigantea fiber: A recyclable oil-absorbing material with large lumens

A facile route was used for improving the oil-absorbing performance of Calotropis gigantea fiber (CGF) via a convenient oxidative polymerization of dopamine in the presence of attapulgite (APT) and subsequent instant immersion in an ethanolic solution of 1H,1H,2H,2H-perfluorooctyltriethoxysilane (PFS). The scanning electron microscope (SEM) coupled with element mapping indicated that the CGF had been successfully modified by polydopamine–APT–PFS, by which a roughened surface with higher contact angle against water can be formed. Consequently, the resulting fiber showed a significant enhancement in the oil-absorbing capacity, with 99.2 g/g for blend oil, 97.7 g/g for soybean oil, and 88.4 g/g for kerosene, respectively. Compared with previous methods, this approach is convenient for the construction of a novel material with tailored morphology and functionality, and the resulting fiber shows its promising application as a highly efficient and recyclable oil-absorbing material for oily wastewater treatment

Anti-atherosclerosis effect of nobiletin via PINK1/Parkin-mediated mitophagy and NLRP3 inflammasome signaling pathway

The incidence of atherosclerosis (AS) is enormously increased, which becomes a serious public health problem. Nobiletin (NOB), a natural active substance of citrus, is found possessed abundant nutritional activities. However, the mechanism of anti-atherosclerosis effect of NOB has not been elucidated. Hences, the purpose of this study was to explore roles for NOB in AS. Macrophages and ApoE-/- mice models were used to investigate the anti-atherosclerotic effect and mechanism of NOB. The results indicated that NOB could modulate blood lipid metabolism and inflammation levels in mice, inhibit the formation of arterial plaques. Additionally, our data showed that mitophagy, inflammatory response, and cell pyroptosis were found in ApoE-/- mice after the treatment by NOB. The expression of key genes of PINK1/Parkin-mediated mitophagy were significantly up-regulated after treatment of NOB, while these of NLRP3 inflammasome were inhibited. Taken together, the underlying mechanism of NOB is to activate PINK1/Parkin-mediated mitophagy and suppress NLRP3-induced inflammasome production to provide an anti-atherosclerotic effect

Polydopamine-clay functionalized <i>Calotropis gigantea</i> fiber: A recyclable oil-absorbing material with large lumens

<p>A facile route was used for improving the oil-absorbing performance of <i>Calotropis gigantea</i> fiber (CGF) via a convenient oxidative polymerization of dopamine in the presence of attapulgite (APT) and subsequent instant immersion in an ethanolic solution of 1H,1H,2H,2H-perfluorooctyltriethoxysilane (PFS). The scanning electron microscope (SEM) coupled with element mapping indicated that the CGF had been successfully modified by polydopamine–APT–PFS, by which a roughened surface with higher contact angle against water can be formed. Consequently, the resulting fiber showed a significant enhancement in the oil-absorbing capacity, with 99.2 g/g for blend oil, 97.7 g/g for soybean oil, and 88.4 g/g for kerosene, respectively. Compared with previous methods, this approach is convenient for the construction of a novel material with tailored morphology and functionality, and the resulting fiber shows its promising application as a highly efficient and recyclable oil-absorbing material for oily wastewater treatment.</p

Association of HLA-DPB1 with scleroderma and its clinical features in Chinese population.

Human leukocyte antigen DPB1 was reported to contain singly nucleotide polymorphisms conferring the strongest susceptibility to systemic sclerosis in Korean population. However, associations of specific DPB1 alleles with SSc vary in different ethnic populations. The aim of this study was to profile DPB1 alleles in Chinese population and to identify specific DPB1 alleles in association with SSc and clinical and serological features of SSc in Han Chinese. A cohort containing 338 patients with SSc and 480 gender-matched and unrelated controls were examined in the study. The HLA-DPB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher's test) from 2×2 tables of allele counts or allele carriers and disease status. Thirty eight DPB1 alleles were found in the cohort. DPB1*05:01 was the most common allele in this cohort. DPB1*03:01 and *13:01 were significantly increased in SSc. DPB1*13:01 association had already been described in other ethnic populations, whereas DPB1*03:01 was specific to Han Chinese patients with SSc. In addition, comparisons between SSc subsets indicated that patients carrying DPB1*03:01 were more likely to develop pulmonary fibrosis, DPB1*04 carriers were increased in SSc patients with anti-centromere autoantibodies and in contrast, SSc patients with homozygous DPB1*05:01 showed an opposite association with marginal significance

Association of the HLA-DRB1 with scleroderma in Chinese population.

Multiple alleles of the Human leukocyte antigen (HLA) DRB1 have been strongly associated with systemic sclerosis (SSc) and its clinical or serological subsets. However, the associations vary in different ethnic populations. To define SSc-risk and/or -protective alleles of HLA-DRB1 in Chinese population, we studied a Han Chinese cohort containing 585 patients with SSc and 458 gender-matched, unrelated controls. The HLA-DRB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher's test) from 2×2 tables of allele frequency and disease status. The major SSc-risk allele subtypes of HLA-DRB1 are the DRB1*15∶02 and *16∶02 in this Chinese cohort. Particularly, DRB1*15∶02 was most significantly associated with anti-centromere autoantibodies (ACA) positive, and DRB1*16∶02 with anti-topoisomerase I autoantibodies (ATA) positive patients. On the other hand, DRB1*01∶01 and *04∶06 were strong SSc-protective alleles in Chinese, especially in patients who were ACA positive and had diffuse cutaneous SSc (dcSSc), respectively. In addition, DRB1*11 and *07∶01 also showed significant association with SSc as a risk for and protection from SSc, respectively, and which is consistent with the studies of Spanish, US Caucasian and Hispanic populations. DRB1*15 was associated with ATA positive Chinese SSc that is consistent with Black South African and Korean SSc. These findings of HLA-DRB1 alleles in association with Chinese SSc provide the growing knowledge of genetics of SSc, and indicate that the genetic heterogeneity among ethnicities may significantly impact the complex trait of SSc

Comparisons between controls and SSc subsets.

*<p>PF =  pulmonary fibrosis; nominal significance <i>p</i> value <0.05; Bonferroni correction for significance was calculated as <i>p</i><0.0013.</p