ARCHIVES OF DERMATOLOGICAL RESEARCH
·
2025
·Vol. 317
·期 1
·1-8
·
IF 2.1
Ma Senlin,Sun Yuxin,Zhou Wenzhen,Yuan Yinuo,Yang Yifan,Zheng Yanchao,Lu Qiuxin,Chen Qingjiang,Ding Mingyue,Wang Guoyan,Chen Mingquan
Bullous pemphigoid (BP) represents an autoimmune blistering disorder that may coexist with acquired hemophilia A (AHA), a rare autoimmune condition arising from the formation of circulating autoantibodies directed against factor VIII (FVIII). The underlying pathomechanisms of BP-AHA remain elusive. This study conducted a retrospective analysis of data from 196 BP patients admitted to our hospital. We have collected serum samples from a recently admitted BP-AHA patient and healthy controls to isolate, screen and identify the potential FVIII inhibitors. The expression and function of lipopolysaccharide-binding protein (LBP) in BP-AHA were further validated by a series of biochemical experiments. The retrospective analysis showed that the activated partial thromboplastin time (APTT) values of seven patients exceeded 33.8 s (normal value) in 196 BP patients. FVIII: C (%) and FVIII inhibitors in the plasma of partial prolonged-APTT patients were significantly altered compared with control group or non-prolonged-APTT group. LBP was identified as a potential inhibitory protein of FVIII. Consistently, a notable alteration in LBP expression was observed in the plasma of BP patients with prolonged-APTT. Moreover, the amount of LBP bound to FVIII in the BP-AHA patient was notably higher than that in control group, which was also markedly reversed after treatment. In vitro experiments finally confirmed that exogenous LBP directly bound to FVIII and significantly inhibited FVIII activity. In conclusion, the incidence of AHA in BP patients may be substantially underestimated, which needs more vigilance towards indicators such as APTT, LBP, and FVIII. LBP emerges as an inhibitory protein of FVIII, indicating the potential involvement in the progression of BP-AHA.
研究领域:
免疫学
·
皮肤病学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
Linling Yu,Qiuhong Zhai,Yan Sun
Our previous studies on protein adsorption to the anion-exchangers of poly(ethylenimine) (PEI)-grafted Sepharose FF found that both adsorption capacity and uptake rate of bovine serum albumin (BSA) increased greatly when the PEI grafting density reached over a critical ionic capacity (cIC) due to the 3D protein binding and occurrence of “chain delivery” of bound proteins. Moreover, by the investigation on the anion-exchangers of diethylaminoethyl (DEAE)-modified and DEAE-dextran-grafted Sepharose FF, we found the unique role of surface ligand in facilitating protein uptake kinetics on dextran-functionalized anion exchangers as the “transfer station” for the “chain delivery” of bound proteins. However, what would be the contribution of surface ligands on the transport of bound proteins on PEI chains at a wide range across cIC, particularly at the lower IC range where no “chain delivery” was present? We have thus designed this research to answer the question. To this purpose, we fabricated three series of PEI-Sepharose FF resins, one without surface ligand (i.e., FF-PEI) and two with surface DEAE modifications at DEAE coupling densities of 60 and 90 mmol/L (i.e., FF-D60-PEI and FF-D90-PEI), and focused on the role of surface DEAE at different PEI densities in BSA adsorption equilibrium and uptake kinetics in a wide IC range of PEI across cIC (∼600 mmol/L for BSA). It was found that, at low grafting-ligand densities (IC cIC, however, both adsorption capacity and uptake rate changed only slightly (<5% and <10%, respectively) by the addition of surface DEAE groups. The results revealed that at IC < cIC, the surface DEAE groups provided the supplement of available binding sites and facilitated the happenings of the “chain delivery” of bound proteins as the “transfer station”, both of which were limited at the low IC range. However, at IC > cIC, the extended flexible PEI chains have already afforded 3D binding space with high accessibility and easy happening of “chain delivery” of bound proteins, so the surface DEAE groups between neighboring PEI chains did not work in assisting the transport of bound proteins. Moreover, when the IC was lower but close to the cIC, the FF-D-PEI resins exhibited higher uptake rates than FF-PEI resins at a similar or even lower IC values. These findings indicate that surface modification of charged groups in PEI-based anion exchangers of low grafting density would be an efficient strategy to fabricate high performance protein ion exchangers.
研究领域:
生物化学
·
分离科学
·
蛋白质工程
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DOI
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2021
·Vol. 195
·期 4
·2432-2450
·
IF 2.926
Zhang Yueqi,Ding Liping,Yan Zhenzhen,Zhou Dandan,Jiang Junwei,Qiu Jiarong,Xin Zhihong
An alkaline esterase, designated as EstXT1, was identified through functional screening from a metagenomic library. Sequence analysis revealed that EstXT1 belonged to the family VIII carboxylesterases and contained a characteristic conserved S-x-x-K motif and a deduced catalytic triad Ser56-Lys59-Tyr165. EstXT1 exhibited the strongest activity toward methyl ferulate at pH 8.0 and temperature 55°C and retained over 80% of its original activity after incubation in the pH range of 7.0–10.6 buffers. Biochemical characterization of the recombinant enzyme showed that it was activated by Zn 2+ and Co 2+ metal ion, while inhibited by Cu 2+ and CTAB. EstXT1 exhibited significant promiscuous acyltransferase activity preferred to the acylation of benzyl alcohol acceptor using short-chain p NP-esters (C2-C8) as acyl-donors. A structure–function analysis indicated that a WAG motif is essential to acyltransferase activity. This is the first report example that WAG motif plays a pivotal role in acyltransferase activity in family VIII carboxylesterases beside WGG motif. Further experiment indicated that EstXT1 successfully acylated cyanidin-3-O-glucoside in aqueous solution. The results from the current investigation provided new insights for the family VIII carboxylesterase and lay a foundation for the potential applications of EstXT1 in food and biotechnology fields.
研究领域:
生物化学
·
生物技术
·
酶学
·
食品科学
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DOI
PubMed
高影响因子
ACS Nano
·
2018
·
IF 13.709
Tao Liu,Mingkang Zhang,Wenlong Liu,Xuan Zeng,Xianlin Song,Xiaoquan Yang,Xianzheng Zhang,Jun Feng
This study reports a family of photothermal materials, metal ion/tannic acid assemblies (MITAs). MITAs from FeIII, VIII, and RuIII afford excellent photothermal efficiency (η ≈ 40%). Sharply differing from the currently existing photothermal agents, MITAs are highlighted by merits including green synthesis, facile incorporation of diagnostic metal ions, and particularly topology-independent adhesion. Owing to the adhesion nature of MITAs, various kinds of MITA-based nanoengineerings are readily available via the self-adhesion of MITAs onto diverse templates, enabling MITAs well suited as a photothermal platform for versatile combination with other therapy approaches and imaging techniques. As a proof of concept, polymeric/inorganic nanoparticle/nanovesicle-supported FeIII-tannic acid (FeIIITA) is fabricated. The photothermal effect is shown to be unaffected by the template origin and type and FeIIITA thickness on the templates. We validate the potency of nanovesicle-supported FeIIITA (PNV@FeIIITA) for tumor-specific photoactivated utilizations, including NIR photothermal therapy with complete tumor elimination, photothermal imaging (PTI), and photoacoustic imaging (PAI) in addition to T1-MRI imaging. PNV@FeIIITA can be simultaneously equipped with functionalities, including T2-MRI imaging by additionally doping MnII and NIR fluorescence imaging by encapsulating a hydrophilic NIR fluoroprobe. MITA demonstrates unparalleled superiority as a photothermal platform in engineering multimodal theranostics for advanced applications.
研究领域:
材料科学
·
纳米技术
·
诊疗学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
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