Analytical Methods
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2024
·Vol. 16
·期 15
·2248-2255
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IF 2.7
Xiaoling Fu,Fan Zhang,Fangda Zhen,Lian Duan,Jian Zhou,Jianguo Ma
Herein, a magnetic bead-based chemiluminescence assay is reported to detect type IV collagen (col-IV) in serum samples. Magnetic beads (MBs) exhibit biocompatibility. Taking advantage of this property, they were conjugated with the col-IV antibody. For the determination of col-IV, the interaction of the col-IV sample, anti-(col-IV)-alkaline phosphatase (anti-(col-IV)-ALP) and anti-col-IV-magnetic beads (anti-(col-IV)-MBs) was performed to generate chemiluminescence. Under the optimized conditions, the developed method displayed good linearity in the concentration range of 20–2000 ng mL−1 with the limit of 0.79 ng mL−1. The repeatability coefficient of variation (CV) for col-IV detection ranged from 3.16% to 7.50%. The col-IV level in samples collected from a hospital was assessed by the chemiluminescence assay. Satisfactory recoveries were obtained ranging from 93.30% to 100.14%. In conclusion, the magnetic bead-based chemiluminescence assay may be used as a routine and efficient tool to detect type IV collagen in clinical diagnosis.
研究领域:
医学诊断
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免疫学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Clinical and Translational Hepatology
·
2024
·Vol. 13
·期 2
·105
·
IF 3.1
Yimeng Zhou,Yang Ding,Yanwei Li,Qiuju Sheng,Chao Han,Yaoxin Fan,Ziyi Wang,Bingchao Lu,Xiaoguang Dou,Chong Zhang
Background and Aims Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms. Methods Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line. Results Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL. Conclusions NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.
研究领域:
医学
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消化系统疾病
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分子生物学
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DOI
PubMed
高影响因子
AQUACULTURE
·
2021
·
IF 4.242
Xiaoxue Yin,Nuo Chen,Liangliang Mu,Hao Bai,Hairong Wu,Weiwei Qi,Yu Huang,Jichang Jian,Anli Wang,Jianmin Ye
Hepcidin (Hepc), as an antimicrobial peptide , plays a vital role in regulating the iron homeostasis and participating in innate immunity. In this study, the open reading frame of Nile tilapia ( Oreochromis niloticus ) hepcidin mRNA ( OnHepc ) was amplified, and its tissue distribution and expression pattern in response to bacterial infection and iron overload were characterized. The results showed that the ORF of OnHepc is 273 bp in length and encodes a peptide with 90 amino acids. Hepcidin has a certain degree of conservation among different species. OnHepc is widely expressed in ten tissues of natural Nile tilapia and is most abundant in the liver. The expression of OnHepc was apparently upregulated in liver, spleen, intestine and gills after challenged by S. agalactiae and A. hydrophila . In addition, the OnHepc expression in MO/Mø and hepatocytes was also upregulated after challenged by the above bacteria. On the other hand, the OnHepc transcripts were upregulated in the liver, spleen, intestine and gills after challenged by 1 μM and 10 μM FeCl 3 solutions, and the same trends were observed in the MO/Mø and hepatocytes after challenged by ferric ions. Moreover, the OnHepc expression was significantly upregulated after stimulated by (r)OnIL-6 protein, suggesting that inflammatory responses regulate the expression of OnHepc . In summary, the present study shows that OnHepc probably gets involved in against bacterial infection and regulating the iron homeostasis in O. niloticus .
研究领域:
鱼类生理学
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免疫学
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分子生物学
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Piao Hu,Haifeng Miao,Mei Li,Ruxue Zhou,Qinqin Lou,Dezhen Wang,Junli Gao,Feng Guo
Hepatitis B virus (HBV) infection represents a major public health challenge due to its potential progression to liver cirrhosis and hepatocellular carcinoma, underscoring the importance of early diagnosis for effective management. This study aimed to identify plasma biomarkers for the non-invasive diagnosis of hepatitis B cirrhosis (HBC). We employed quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry on plasma samples from 27 individuals, including 13 patients with HBC and 14 with chronic hepatitis B (CHB). Bioinformatics analysis of 963 identified proteins revealed 234 differential expressed proteins, comprising 115 upregulated and 119 downregulated proteins. Four candidate biomarkers—CHI3L1, IGFBP1, SHBG, and TIMP2—were subsequently selected and validated using ELISA in a cohort of 158 patients, all demonstrating elevated levels in HBC patients. The four-biomarker panel (4MP) demonstrated superior diagnostic performance, achieving an area under the curve (AUC) of 0.902 for distinguishing HBC from CHB. For differentiating decompensated HBC from CHB, the 4MP achieved an AUC of 0.993, with a sensitivity of 93.75% and specificity of 98.73%. Mostly, the 4MP also performed well in identifying severe HBC from non-severe HBC, achieving an AUC of 0.911, with a sensitivity of 93.75% and specificity of 98.73%. In conclusion, this study identifies four novel plasma biomarkers for HBC, highlighting their potential to enhance non-invasive diagnostic strategies for monitoring HBC progression.
研究领域:
医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
LIVER INTERNATIONAL
·
2025
·Vol. 45
·期 3
·e70024
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IF 5.2
Guqing Luo,Zhenghao Wu,Qiang Fan,Chihao Zhang,Jiayun Lin,Hongjie Li,Jinbo Zhao,Haizhong Huo,Xiaoliang Qi,Guangbo Wu,Min Chen,Jiwei Yu,Lei Zheng,Meng Luo
Background and Aims Lymphangiogenesis is enhanced during the development of liver cirrhosis and portal hypertension (PHT). However, hepatic lymphatic vascular system is understudied in liver cirrhosis and PHT. Hydrogen sulfide (H 2 S) and related compounds have potential prolymphangiogenic effects besides its previously reported vascular-protective effects. Therefore, we aimed to investigate the effects of endogenous H 2 S donor S-allyl-cysteine (SAC) on bile duct ligation (BDL)-induced liver cirrhosis and PHT. Methods BDL rats with cholestatic liver cirrhosis and PHT were orally administrated with SAC at 100 or 200 mg/kg/day, as well as DL-propargylglycine (PAG) or MAZ-51 injections. Hemodynamic parameters were determined, and subsequent evaluations of liver fibrosis, intrahepatic vascular resistance (IHVR) and lymphangiogensis were performed. Human lymphatic endothelial cells (hLECs) were used for in vitro verification of prolymphangiogenic effects of SAC. Results SAC treatment significantly decreased PP and promoted endogenous H 2 S production. Liver fibrosis and IHVR were also ameliorated. Hepatic and mesenteric lymphangiogenesis were enhanced in BDL rats and further promoted by SAC despite a significant downregulation of hepatic VEGF-C. Inhibition of H 2 S production by PAG significantly reduced lymphatic vessels, while inhibition of lymphangiogensis by MAZ-51 reversed the protective effects of SAC against PHT. SAC enhanced lymphangiogenic functions in vitro by promoting cellular H 2 S production and activating Akt phosphorylation without altering VEGF-C/D, which were reversed by PAG and MAZ-51. Conclusions SAC significantly alleviated BDL-induced liver cirrhosis and PHT. Meanwhile, elevated H 2 S induced by SAC facilitated lymphangiogenesis via a VEGF-C-independent manner, which contributed to the alleviation of PHT.
研究领域:
医学
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药理学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-11
·
IF 5.228
Wei Yushuang,Zhao Mengzhu,Yang Fang,Mao Yang,Xie Hang,Zhou Qibing
Superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent have been widely used in magnetic resonance imaging for tumor diagnosis and theranostics. However, there has been safety concern of SPIONs with cirrhosis related to excess iron-induced oxidative stress. In this study, the impact of iron overload by SPIONs was assessed on a mouse cirrhosis model. A single dose of SPION injection at 0.5 or 5 mg Fe/kg in the cirrhosis group induced a septic shock response at 24 h with elevated serum levels of liver and kidney function markers and extended impacts over 14 days including high levels of serum cholesterols and persistent low serum iron level. In contrast, full restoration of liver functions was found in the normal group with the same dosages over time. Analysis with PCR array of the toxicity pathways revealed the high dose of SPIONs induced significant expression changes of a distinct subset of genes in the cirrhosis liver. All these results suggested that excess iron of the high dose of SPIONs might be a risk factor for cirrhosis because of the marked impacts of elevated lipid metabolism, disruption of iron homeostasis and possibly, aggravated loss of liver functions.
研究领域:
医学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
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2019
·Vol. 9
·期 25
·14051-14059
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IF 3.049
Abdulrahman Ahmed Mahmood,Jianqi Zhang,Rufang Liao,Xiwei Pan,Dan Xu,Haibo Xu,Qibing Zhou
Superparamagnetic iron oxide nanoclusters (SPIONs) modified with pH (low) insertion peptide (pHLIP) could be advantageous for magnetic resonance imaging (MRI) diagnosis of liver tumors at the early stage due to their unique responsiveness to the tumor acidic microenvironment when tumor markers are unknown. However, many critical aspects including the effectiveness of selective MRI in liver tumors, types of delivery and the potential safety profile in cirrhosis need to be fully evaluated. In this study, we report the evaluation of non-targeting, C- or N-pHLIP modified SPIONs as the contrast agent for selective MRI of liver tumors and their potential toxicity profile in cirrhosis. It was found that N-pHLIP modified SPIONs did not result in the loss of liver tumor in the T2-weight MRI but provided additional dynamic details of tumor structures that would enhance the diagnosis of liver tumors at a small size below 8 mm. In addition, an enhanced safety profile was found for N-pHLIP modified SPIONs with almost fully recoverable impact in cirrhosis. In contrast, the poly-D-lysine assembled SPIONs and C-terminus linked pHLIP SPIONs had non-tumor specific MRI contrast enhancement and potential safety risks in cirrhosis due to the iron overload post injection. All these results implied the promising potential of N-terminus linked pHLIP SPIONs as an MRI contrast agent for the diagnosis of liver tumors.
研究领域:
医学影像学
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纳米技术
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药理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Ming Luo,Yawei Du,Xuanchen Liu,Shuwen Zhang,Wenwen Zhu,Kaipeng Liu,Xiubao Ren,Ningning Zhang
Background Portal hypertension (PHT) is a severe complication of liver cirrhosis, with limited therapeutic options. Despite emerging evidence linking gut microbiota dysbiosis to PHT progression, the mechanisms by which microbial metabolites modulate liver sinusoidal endothelial cells (LSECs) dysfunction and the therapeutic efficacy of fecal microbiota transplantation (FMT) remain poorly understood. This study investigated the potential of FMT to alleviate PHT in cirrhotic rats, exploring the underlying mechanisms involving butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation in LSECs. Methods Cirrhosis with PHT was induced in Sprague-Dawley rats via intraperitoneal carbon tetrachloride injection, followed by FMT or butyrate supplementation via oral gavage. Analyses included portal hemodynamic measurements, gut microbiota sequencing, serum SCFA metabolomics profiling, HDAC3 activity assays, NO level quantification, and assessments of liver fibrosis, liver function, and LSEC ultrastructure. LSECs were isolated for PI3K/Akt/eNOS signaling analysis via qRT-PCR, Western blotting, and immunofluorescence staining. Results A two-week FMT intervention in cirrhotic rats with PHT enriched butyrate-producing bacteria and increased serum butyrate levels, which were associated with reduced portal pressure and intrahepatic vascular resistance, without affecting liver fibrosis, function, or LSEC ultrastructure. FMT reduced HDAC3 activity by 2.17-fold and increased Akt and eNOS phosphorylation in primary LSECs by 1.69-fold and 1.25-fold, respectively, elevating plasma NO levels by 1.66-fold compared to untreated controls. In vitro experiments with primary LSECs confirmed these butyrate-mediated effects. Conclusion FMT alleviates cirrhotic PHT through butyrate-mediated HDAC3 inhibition and subsequent PI3K/Akt/eNOS signaling activation in LSECs, highlighting the therapeutic potential of targeting the gut-liver axis via microbial metabolites for PHT management.
研究领域:
医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 17
·期 1
·393-397
·
IF 1.41
Rendong Wei,Haidong Liu,Ru Chen,Yunjian Sheng,Tao Liu
Astragaloside Ⅳ (AS‑Ⅳ) in improving liver cirrhosis injury in rats and its effect on the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway were observed. Rat model of liver cirrhosis was induced by injection of carbon tetrachloride (CCl4). A total of 36 Sprague‑Dawley (SD) rats were randomly divided into three groups: the normal control group (n=10), the model control group (n=13), and the AS‑Ⅳ group (n=13). The normal control group was injected with olive oil and given carboxymethyl cellulose (CMC)‑Na (10 ml/kg/day), the model control group was given CMC‑Na (10 ml/kg/day), and the AS‑Ⅳ group underwent intragastric administration of AS‑Ⅳ (20 ml/kg/day). The content of alanine transaminase (ALT) and aspartate transaminase (AST) of rats was detected. The levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6 and IL‑1β in serum were detected via enzyme‑linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was applied to observe morphological changes in liver tissues. The expression of collagens in liver tissues was detected via Masson's trichrome staining. Additionally, the expression of proteins in liver tissues was detected via western blotting. Compared with those in the blank group, the levels of AST, ALT, TNF‑α, IL‑6 and IL‑1β were higher, the expression level of collagens in liver tissues was increased, and the expression ratios of phosphorylated (p)‑PI3K/PI3K, p‑Akt/Akt and p‑mTOR/mTOR proteins were increased in the model group. Compared with the model group, AS‑Ⅳ could significantly decrease the content of AST, ALT, TNF‑α, IL‑6 and IL‑β in serum of rats, obviously inhibit the expression of collagens in liver tissues and decrease the expression ratios of p‑PI3K/PI3K, p‑Akt/Akt and p‑mTOR/mTOR proteins in liver tissues. AS‑Ⅳ can inhibit the inflammatory response so as to reduce the expression of collagens, and its mechanism may play a key role by inhibiting the PI3K/Akt/mTOR signaling pathway.
研究领域:
药理学
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肝病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NATURE MEDICINE
·
2025
·
IF 50
He Xiaolong,Hu Mengyao,Xu Yi,Xia Fangbo,Tan Yang,Wang Yuqing,Xiang Huiling,Wu Hao,Ji Tengfei,Xu Qian,Wang Lei,Huang Zhenhe,Sun Meiling,Wan Yu,Cui Peng,Liang Shaocong,Pan Yuan,Xiao Siyu,He Yan,Song Ruixin,Yan Junqing,Quan Xin,Wei Yingge,Hong Changze,Liao Weizuo,Li Fuli,El-Omar Emad,Chen Jinjun,Qi Xiaolong,Gao Jie,Zhou Hongwei
Up to 50–70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut–brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus , increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus . Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut–liver–brain axis and identify a promising therapeutic and predictive target for HE.
研究领域:
胃肠病学
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微生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Cancer Cell International
·
2022
·Vol. 22
·期 1
·1-18
·
IF 6.429
Wang Shunxi,Chen Long,Liu Wanqian
Background Ferroptosis have been implicated in tumorigenesis, tumor progression, and chemo- and immuno-therapy in cirrhotic hepatocellular carcinoma (HCC), indicating its association with matrix stiffness and clinical benefit of targeting drugs or immune checkpoint inhibitor. Here, we postulated that increased matrix stiffness reduces ferroptosis and impairs tumor immunity by regulating the expression of ferroptosis- and immune-related genes in HCC, which might be a robust predictor of therapeutic efficacy. Methods Using publicly available tissue microarray datasets, liver cancer rat model, and clinical specimen, ferroptosis-related differential genes in HCV-infected cirrhotic HCC and its mechanical heterogeneous pattern of expression were screened and identified. Further investigation on the underlying mechanism of matrix stiffness-regulated ferroptosis and the expression of immune mediator were performed. Finally, threshold analysis of HCC cases with sorafenib treatment revealed the value of clinical applications of these potential predictors. Results STEAP3 was identified as the ferroptosis-related differential genes in HCV-infected cirrhotic HCC. Stiffer matrix decreased STEAP3 in the invasive front area of HCC and the liver cirrhotic tissue. Contrarily, softer matrix induced STEAP3 in the central area of HCC and the normal liver tissue. Immunological correlation of STEAP3 in cirrhotic HCC showed that STEAP3-mediated immune infiltration of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells and HCC prognosis, predicting to regulate immune infiltration. Overexpression of STEAP3 induced ferroptosis and inhibited the expression of immune mediator of PD-L2 on a stiff matrix. Especially, the ferroptosis- and immune-related gene predictive biomarker (FIGPB), including STEAP3 and PD-L2, predicts better clinical benefit of sorafenib in HCC patients. Conclusions This finding identifies matrix stiffness impairs ferroptosis and anti-tumor immunity by mediating STEAP3 and PD-L2. More importantly, coordinated with PD-L2, matrix stiffness-dependent STEAP3 could be applied as the independent predictors to favorable sorafenib response, and thus targeting it could be a potential diagnosis and treatment strategy for HCC.
研究领域:
肿瘤学
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免疫学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Ruixi Li,Qiang Tao,Jiandong Zha,Shikai Wang,Xiaozhun Huang,Jicai Wang,Hang Zhai,Shengjie Hong,Guangquan Zhang
Currently, suppressing macrophage M1 polarization and HSC activation are recognized as potential therapeutic strategies for liver cirrhosis. Ubiquitin-like with PHD and RING Finger Domains 1 (UHRF1) is a crucial epigenetic modulator implicated in maintaining DNA methylation and chromatin structure. Knockdown of high mobility group A protein 2 (HMGA2) was reported to ameliorate hepatic inflammation and fibrosis in nonalcoholic fatty liver disease. Here, the elaborate effect of UHRF1-mediated HMGA2 promoter methylation was investigated during the progression of liver cirrhosis. Transcriptomic sequencing of liver tissues of cirrhotic patients was carried out and a mouse model with liver cirrhosis was established by intraperitoneal injection of carbon tetrachloride (CCl 4 ) twice weekly for four consecutive weeks. Lipopolysaccharide (LPS)-induced RAW264.7 were transduced with overexpressed UHRF1 adenovirus and cell supernatant was applied as the conditional medium to cultivate hepatic stellate cells (HSCs). Notably, in vivo experiments, enhanced UHRF1 expression alleviated fibrosis and inflammation of mouse livers. In vitro experiments, upregulated UHRF1 suppressed CCl 4 -stimulated macrophage M1 polarization and HSC activation. Moreover, MSP assay revealed that methylation was enhanced on HMGA2 promoter at −599/2−450 site after UHRF1 overexpression. More intriguingly, ChIP and Co-IP results clarified that UHRF1 interacted with DNA methyltransferase 1 (DNMT1), thereby bound to HMGA2 promoter and facilitated its methylation. Furthermore, increased HMGA2 level abolished the inhibitory effects of UHRF1 upregulation on the mRNA expression of pro-inflammatory genes of macrophages and genes encoding collagen of HSCs. Collectively, UHRF1 weakened HMGA2 expression by catalyzing its promoter methylation, thereby blocked macrophage M1 polarization and mitigated liver cirrhosis.
研究领域:
分子生物学
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表观遗传学
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肝脏病学
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免疫学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）