ACT001 alleviates inflammation and pyroptosis through the PPAR-γ/NF-κB signaling pathway in LPS-induced alveolar macrophages

Fu Qiang,Shen Na,Fang Tao,Zhang Hewei,Di Yanbo,Liu Xuan,Du Chao,Guo Jianshuang 한국유전학회 2024 Genes & Genomics Vol.46 No.3

Background ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known. Objective The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages. Methods NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor. Results Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed. Conclusion ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages. Background ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known. Objective The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages. Methods NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor. Results Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed. Conclusion ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages.

Complete Mitochondrial Genome of Echinostoma hortense (Digenea: Echinostomatidae)

Ze-Xuan Liu,Yan Zhang,Yu-Ting Liu,Qiao-Cheng Chang,Xin Su,Xue Fu,Dong-Mei Yue,Yuan Gao,Chun-Ren Wang 대한기생충학열대의학회 2016 The Korean Journal of Parasitology Vol.54 No.2

Molecular cloning of novel α-gliadin genes from Crithopsis delileana and the evolution analysis with those from Triticeae

Zhi-Fu Guo,Xiang-Yu Long,Pan Dong,Yu-Ming Wei,Li-Ping Bai,Xiao-Xuan Dang,Hao-Lei Wan,Li-Jun Zhang,You-Liang Zheng 한국유전학회 2011 Genes & Genomics Vol.33 No.2

The α-gliadins from Crithopsis delileana (Schult) Roshev (2n=2x=14, KK) were investigated by Acid polyacrylamide gel electrophoresis (A-PAGE) analysis. It was indicated that the electrophoresis mobility of gliadins from C.delileana had obvious difference with those from common wheat in α, γand ω region. Using primers designed from published sequences of α-gliadin genes, three α-gliadin genes were isolated from C. delileana, which were designated as gli-ka1,gli-ka2 and gli-ka3, respectively. Two in-frame stop codons were found in the coding sequences of gli-ka3, indicating that gli-ka3 could be a pseudogene. The gli-ka2 was a gliadin with an odd number of cysteines, resulting from a non-synonymous mutation. This change might lead to the interactive behavior of gli-ka2. Three α-gliadin genes of C. delileana had the similar but not identical primary structures to the corresponding gene sequences from other wheat related species. By the alignment of α-gliadin genes from Triticeae,phylogenetic analysis indicated that three α-gliadin genes of C. delileana clustered together with all α-gliadin genes from Ee genome of Lophopyrum elongatum by an interior paralleled branch.

Correlation between the Position of the Pituitary Stalk as Determined by Diffusion Tensor Imaging and Its Location as Determined at the Time of Surgical Resection of Pituitary Adenomas

Wang, Fu-yu,Wang, Peng,Yang, Chen-xuan,Zhou, Tao,Jiang, Jin-li,Meng, Xiang-hui The Korean Neurosurgical Society 2020 Journal of Korean neurosurgical society Vol.63 No.4

Objective : An important factor during pituitary adenoma surgery is to preserve pituitary stalk (PS) as this plays a role in reduction of the risk of postoperative diabetes insipidus. The hypothalamic-hypophyseal tract (HHT) projects through the PS to the posterior pituitary gland. To reconstruct white matter fiber pathways, methods like diffusion tensor imaging (DTI) tractography have been widely used. In this report we attempted to predict the position of PS using DTI tractography and to assess its intraoperative correlation during surgery of pituitary adenomas. Methods : DTI tractography was used to tract the HHT in nine patients before craniotomy for pituitary adenomas. The DTI location of the HHT was compared with the PS position identified at the time of surgery. DTI fiber tracking was carried out in nine patients prior to the planned craniotomy for pituitary adenomas. In one patient, the PS could not be identified during the surgery. In the other eight patients, a comparison was made between the location of the HHT identified by DTI and the position of the PS visualized at the time of surgery. Results : The position of the HHT identified by DTI showed consistency with the intraoperative position of the PS in seven patients (88.9% concordance). Conclusion : This study shows that DTI can identify the position of the HHT and thus the position of the PS with a high degree of reliability.

Mechanical evaluation of polymer microneedles for transdermal drug delivery: In vitro and in vivo

Rui Xuan Liu,Yu Ting He,Ling Liang,Liu Fu Hu,Yue Liu,Rui-xing Yu,Bo Zhi Chen,Yong Cui,Xin Dong Guo 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.114 No.-

In this study, we reported two types of PMNs based on polylactic acid (PLA) and polyvinyl alcohol (PVA),respectively. Parafilm M film, porcine skin, and rats’ models were operated to evaluate the mechanicalproperties in vitro and in vivo to find optimal parameters for efficient insertion. Insertion depth was measuredusing Digital Force Gauge by changing insertion force and speed, respectively. Results showed thatincreasing the insertion force and speed used for PMNs application led to a significant increase in thedepth of insertion. A force of 18 N under a speed of 330 mm/min was the optimal condition for insertingPMNs array into ParafilmM film and porcine skin. In addition, PLA-MNs exhibited higher robustness andenhanced homogeneity in insertion depth compared with PVA-MNs, but PVA-MNs were able to reachmuch deeper insertion depth. Moreover, Sprague Dawley (SD) rat experiments confirmed the effectivenessof optimal insertion parameters for transdermal drug delivery. This study illustrated not only thedevelopment of novel PMNs but also the mechanical evaluation for the design of PMNs.

Sequential Polyadenylation to Enable Alternative mRNA 3’ End Formation

Xiang-Dong Fu,Yajing Hao,Ting Cai,Chang Liu,Xuan Zhang 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.1

In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3′ end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3′ ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3′UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered “apparent” APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism to provide insights into various documented regulatory paradigms.

클러스터 분석을 이용한 황련 추출물 항산화 활성 최적화 추출공정

부민민 ( Minmin Fu ),현송화 ( Song Hua Xuan ),박수남 ( Soo Nam Park ) 한국공업화학회 2018 공업화학 Vol.29 No.5

황련은 여러 가지 질병 치료에 사용되는 효과적인 전통약용식물이다. 하지만 황련 추출물의 생리활성성분 함량에 영향을 미치는 주요 인자 및 생리활성성분과 항산화 효능의 상관관계는 아직 알려지지 않았다. 따라서 본 논문에서는 용매, 온도 및 추출 시간이 황련 추출물의 생리 활성성분의 함량과 항산화 활성에 미치는 영향을 조사하였다. 클라스터를 이용하여 분석한 결과, 35 ℃에서 추출시간 30 min인 에탄올(50% 에탄올 : 50% 물) 조건으로 추출 시, 생리활성 성분 함량 및 항산화 활성이 제일 높으므로 공장에서 사용하기에 가장 적합한 추출조건임을 확인하였다. 다중선형회귀분석 결과, 총 페놀화합물 함량은 DPPH소거 활성에 기여하였으며 총 알칼로이드 함량과 총 플라보노이드 함량은 FRAP활성에 기여하였다. 이상의 결과들로부터 황련의 추출 조건이 생리 활성 화합물의 수율 및 항산화 활성을 조절 가능하며, 이는 공업적인 응용에 중요한 정보를 제공할 수 있을 것으로 사료된다. Coptis chinensis Franch is a valuable traditional oriental medicinal plant used for the treatment of various diseases. The major factors affecting the content of bioactive compounds and the relationship between bioactive compounds and antioxidant capacities of Coptis chinensis Franch were poorly understood. Thus, effects of the solvent, temperature, and extraction time on the extraction yields of bioactive compounds and the antioxidant activity of C. chinensis Franch extracts were investigated in this work. Our cluster analysis indicated that the hydroalcoholic solvent (50% ethanol : 50% water) at 35 ℃ for 30 min (extract time) was the best extraction condition for a factory use because the highest level of bioactive compounds and antioxidant activities was achieved. Multiple linear regression analysis revealed that total phenolic content (TPC) contributed to the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity, while both total alkaloid content (TAC) and total flavonoid content (TFC) were responsible for ferric reducing antioxidant power (FRAP) activity. These results indicated that extraction conditions controlled the yield of bioactive compounds and the antioxidant activity of C. chinensis Franch, which can provide important information for the industrial extraction.

Cat NPC2, a Newly Identified Allergen, With High Cross-Reactivity to Can f 7

Zhu Dan-Xuan,Li Lin,Xu Zhi-Qiang,Zhang Cheng,Zhang Jin-Song,Sun Jin-Lyu,Wei Ji-Fu 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.1

Purpose: Pet-derived allergens are the common indoor inhalant allergens. Among them, cat and dog allergens constitute more than 80% of animal allergic patients, which greatly affect the quality-of-life of patients and increase the burden of social health care. The aim of this study was to identify Cat-Niemann pick type C2 (NPC2) protein, a homologue of Can f 7, as a new allergen. Methods: Cat-NPC2 complementary DNA (cDNA) was cloned and optimized for amplification and expression in Escherichia coli. Then, recombinant Cat-NPC2 (rCat-NPC2) was purified by Ni2+ affinity chromatography. The allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), western blot and basophil activation test (BAT). Based on the sequence similarity, the cross-reactivity between Cat-NPC2 and Can f 7 was investigated by inhibition ELISA. Circular dichroism spectroscopy and homology modeling were used to characterize the structure of Cat-NPC2. Results: The cDNA sequence of Cat-NPC2 was cloned with a 450-bp open reading frame coding for 149 amino acids (GenBank MN_737596). The condon-optimized NPC2 gene was subcloned and expressed in E. coli with a molecular weight of 18.9 kDa. The native Cat-NPC2 was detected in cat dander extracts. The allergenicity determined by ELISA, western blot and BAT suggested at least 14.5% cat-allergic patients displayed high specific immunoglobulin E (IgE) recognition of Cat-NPC2. The predicted structure of Cat-NPC2 was found to consist of 7 β-strands arranged in 2 β-sheets. An ELISA based assay showed that rCat-NPC2 bound to cholesterol in a dose dependent manner. Based on the structure and sequence similarities, IgE cross-reactivity was demonstrated between Cat-NPC2 and Can f 7/Der f 2. Conclusions: In the study, a novel cat allergen, belonging to the NPC2 protein family, was identified and characterized at both molecular and immunological levels. The study will offer a deeper understanding of cat allergens and improve a component-resolved diagnosis in pet allergy.

Metabolism of dl-Praeruptorin A in Rat Liver Microsomes using HPLC-Electrospray Ionization Tandem Mass Spectrometry

Hang Ruan,Xuan Zhu,Zhen Zhang,Xin-fang Liang,Yan Fu,Mei-qin Su,Qi-lin Liu,Xiu-min Wang 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.8

dl-Praeruptorin A (Pd-Ia) is the major active constituent of the traditional Chinese medicine Peucedanum praeruptorum Dunn. Recently it has been identified as a novel agent in the treatment and prevention of cardiovascular diseases. Accordingly, we investigated the metabolism of Pd-Ia in rat liver microsomes. The involvement of cytochrome P450 (CYP) and CYP isoforms were identified using a CYP-specific inhibitor (SKF-525A), CYP-selective inhibitors (α-naphthoflavone, metyrapone, fluvastatin, quinidine, disulfiram, ketoconazole and ticlopidine) and CYP-selective inducers (phenobarbital, dexamethasone and β-naphthoflavone). Residual concentrations of the substrate and metabolites were determined by HPLC, and further identified by their mass spectra and chromatographic behavior. These experiments showed that CYP450 is involved in Pd-Ia metabolism, and that the major CYP isoform responsible is CYP3A1/2, which acts in a concentration-dependent manner. Four Pd-Ia metabolites (M1, M2, M3, and M4) were detected after incubation with rat liver microsomes. Hydroxylation was the primary metabolic pathway of Pd-Ia, and possible chemical structures of the metabolites were identified. Further research is now needed to link the metabolism of Pd-Ia to its drug-drug interactions.

Novel Schemes to Optimize Sampling Rate for Compressed Sensing

YiFan Zhang,Xuan Fu,Qixun Zhang,Zhiyong Feng,Xiaomin Liu 한국통신학회 2015 Journal of communications and networks Vol.17 No.5

The fast and accurate spectrum sensing over an ultra- wide bandwidth is a big challenge for the radio environment cogni- tion. Considering sparse signal feature, two novel compressed sens- ing schemes are proposed, which can reduce compressed sampling rate in contrast to the traditional scheme. One algorithm is dynam- ically adjusting compression ratio based on modulation recogni- tion and identification of symbol rate, which can reduce compres- sion ratio. Furthermore, without priori information of the modu- lation and symbol rate, another improved algorithm is proposed with the application potential in practice, which does not need to reconstruct the signals. The improved algorithm is divided into two stages, which are the approaching stage and the monitoring stage. The overall sampling rate can be dramatically reduced with- out the performance deterioration of the spectrum detection com- pared to the conventional static compressed sampling rate algo- rithm. Numerous results show that the proposed compressed sens- ing technique can reduce sampling rate by 35%, with an acceptable detection probability over 0.9.