scholarly journals Serum Exosomal miRNAs for Grading Hepatic Fibrosis Due to Schistosomiasis

2020 ◽  
Vol 21 (10) ◽  
pp. 3560
Author(s):  
Pengfei Cai ◽  
Yi Mu ◽  
Remigio M. Olveda ◽  
Allen G. Ross ◽  
David U. Olveda ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Expression Profiles ◽  
Serum Levels ◽  
Current Data ◽  
Schistosomiasis Japonica ◽  
Temporal Expression ◽  
Ribonucleic Acids ◽  
Need For Treatment ◽  
Exosomal Mirnas

Chronic infection with Schistosoma japonicum or Schistosoma mansoni results in hepatic fibrosis of the human host. The staging of fibrosis is crucial for prognosis and to determine the need for treatment of patients with schistosomiasis. This study aimed to determine whether there is a correlation between the levels of serum exosomal micro-ribonucleic acids (miRNAs) (exomiRs) and fibrosis progression in schistosomiasis. Reference gene (RG) validation was initially carried out for the analysis of serum exomiRs expression in staging liver fibrosis caused by schistosome infection. The expression levels of liver fibrosis-associated exomiRs in serum were determined in a murine schistosomiasis model and in a cohort of Filipino schistosomiasis japonica patients (n = 104) with different liver fibrosis grades. Of twelve RG candidates validated, miR-103a-3p and miR-425-5p were determined to be the most stable genes in the murine schistosomiasis model and subjects from the schistosomiasis-endemic area, respectively. The temporal expression profiles of nine fibrosis-associated serum exomiRs, as well as their correlations with the liver pathologies, were determined in C57BL/6 mice during S. japonicum infection. The serum levels of three exomiRs (miR-92a-3p, miR-146a-5p and miR-532-5p) were able to distinguish subjects with fibrosis grades I-III from those with no fibrosis, but only the serum level of exosomal miR-146a-5p showed potential for distinguishing patients with mild (grades 0–I) versus severe fibrosis (grades II–III). The current data imply that serum exomiRs can be a supplementary tool for grading liver fibrosis in hepatosplenic schistosomiasis with moderate accuracy.

scholarly journals Sedum sarmentosum Total Flavonoids Alleviate Schistosomiasis-Induced Liver Fibrosis by Altering TGF-β1 and Smad7 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Peng-chun Yang ◽  
Wei-zhe Bai ◽  
Jing Wang ◽  
Cai-hua Yan ◽  
Wei-feng Huang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Protein Expression ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Schistosomiasis Japonica ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Tgf Β1 ◽  
Liver Tissues

Objectives. Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. Sedum sarmentosum total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism. Methods. Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also measured the expression of transforming growth factor-beta 1 (TGF-β1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry. Results. Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis ( P < 0.05 ). Each dose of SSTF also significantly reduced TGF-β1 protein expression and mRNA levels in the liver tissues ( P < 0.05 ). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels ( P < 0.05 ). Immunohistochemistry showed that each dose of SSTF reduced TGF-β1 protein expression ( P < 0.05 ). Conclusion. Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-β1/Smad7 pathway.

scholarly journals The Dynamics of Hepatic Fibrosis Related to Schistosomiasis and Its Risk Factors in a Cohort of China

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1532
Author(s):  
Fei Hu ◽  
Shu-Ying Xie ◽  
Min Yuan ◽  
Yi-Feng Li ◽  
Zhao-Jun Li ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Infection Rate ◽  
Protective Factor ◽  
Schistosomiasis Japonica ◽  
Active Infection ◽  
Schistosomiasis Control ◽  
Advanced Schistosomiasis ◽  
Endemic Areas ◽  
Thick Smear

China has had a long history against schistosomiasis japonica. The most serious prognosis of chronic schistosome infection is hepatic fibrosis, which develops into advanced schistosomiasis if the process is not effectively controlled. After a more than seven decades endeavor, China has gained remarkable achievements in schistosomiasis control and achieved transmission control nationwide (infection rate of schistosomes in residents and domestic animals both less than 1%) by 2015. However, new advanced schistosomiasis cases emerge annually in China, even in areas where the transmission of schistosomiasis had been interrupted. In the present study, the residents (>5 years old) in a schistosomiasis endemic village were examined for schistosomiasis every year during 1995–2019 by the modified Kato–Katz thick smear method and/or miracidium hatching technique. Residents who were identified to have an active infection method were treated with praziquantel at a dose of 40 mg/kg body weight. Ultrasonography was carried out to assess the liver morbidity related to schistosomiasis in 1995 and 2019, respectively. The prevalence of schistosomiasis among residents presented a downward trend annually, from 17.89% (175/978) in 1995 to 0 (0/475) in 2019. Among 292 residents who received ultrasound scan both in 1995 and 2019, 141 (48.29%) presented stable liver damage, while liver fibrosis was developed severely in 86 (29.45%) and reversed in 65 (22.26%) residents. Univariate and multivariate analysis showed that anti-fibrosis treatment was the protective factor against schistosomiasis hepatic fibrosis. Males, residents aged 38 and above, fishermen, and people who did not receive anti-fibrosis treatment were groups with higher risk of liver fibrosis development. Our results revealed that although the infection rate of schistosome dropped significantly in endemic areas, liver fibrosis was still developing among some residents, even though they had received deworming treatment. Liver protection/anti-fibrosis treatment should be administered in endemic regions and regions with historically uncontrolled transmission to slow down the deterioration of hepatic fibrosis among patients in schistosomiasis endemic areas.

Irisin ameliorates endoplasmic reticulum stress and liver fibrosis through inhibiting PERK-mediated destabilization of HNRNPA1 in hepatic stellate cells

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Xin Liao ◽  
Wei Zhan ◽  
Rui Li ◽  
Tian Tian ◽  
Lei Yu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Fibrosis ◽  
Er Stress ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Elevated Serum ◽  
Stellate Cells ◽  
Serum Levels ◽  
Beneficial Effects ◽  
The Stability

Abstract Liver fibrosis is a common consequence of chronic liver diseases involved with the activation of hepatic stellate cells (HSCs) and endoplasmic reticulum (ER) stress. Irisin is a small polypeptide hormone that shows beneficial effects on metabolic disorders. The current study aimed to investigate the biological function of irisin on hepatic fibrosis. A mouse model of carbon tetrachloride (CCl4)-induced hepatic fibrosis was established. CCl4-treated mice showed elevated serum levels of AST and ALT, increased collagen accumulation, induced ER stress, and upregulated expressions of pro-fibrotic proteins in the liver compared to the controls. The administration of irisin, however, ameliorated CCl4-induced hepatic fibrosis in both cultured HSCs and mice. PKR-like ER kinase (PERK) is a key component of the ER stress-associated signaling pathway. We found that irisin treatment improved the stability of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) via regulating the phosphorylation of PERK in mouse livers and isolated HSCs. Also, the knockdown of HNRNPA1 eliminated the hepatoprotective effects of irisin on hepatic fibrosis and ER stress. In summary, this study showed that irisin alleviated ER stress and hepatic fibrosis by inhibiting PERK-mediated HNRNPA1 destabilization, suggesting that irisin may represent a promising therapeutic strategy for patients with liver fibrosis.

scholarly journals Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hafiz Muhammad Umer Farooqi ◽  
Bohye Kang ◽  
Muhammad Asad Ullah Khalid ◽  
Abdul Rahim Chethikkattuveli Salih ◽  
Kinam Hyun ◽  
...  
Keyword(s):  
Cell Culture ◽  
Liver Fibrosis ◽  
Real Time ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Cell Monolayer ◽  
Embedded Sensors ◽  
Matrix Deposition ◽  
Tgf Β1

AbstractHepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

scholarly journals Total Antioxidant Capacity in HBV Carriers, a Promising Biomarker for Evaluating Hepatic Fibrosis: A Pilot Study

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Jing-Hua Wang ◽  
Sung-Bae Lee ◽  
Dong-Soo Lee ◽  
Chang-Gue Son
Keyword(s):  
Oxidative Stress ◽  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Antioxidant Capacity ◽  
Chronic Hepatitis B ◽  
Hepatic Fibrosis ◽  
Total Antioxidant Capacity ◽  
Hbv Dna ◽  
Total Antioxidant

Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = −0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers.

Temporal expression profiles of defense-related genes involved in Lactuca sativa- Sclerotinia sclerotiorum interactions

2021 ◽  
Author(s):  
Aqeel Hussein Abdulraoof Almatwari ◽  
Mohammadreza Hassandokht ◽  
Frouzandeh Soltani ◽  
Amir Mirzadi Gohari ◽  
Mohammad Javan-Nikkhah
Keyword(s):  
Sclerotinia Sclerotiorum ◽  
Lactuca Sativa ◽  
Expression Profiles ◽  
Temporal Expression

Dynamic computed tomography with low- and high-molecular-mass contrast agents to assess microvascular permeability modifications in a model of liver fibrosis

2002 ◽  
Vol 103 (2) ◽  
pp. 213-216 ◽  
Author(s):  
Roland MATERNE ◽  
Laurence ANNET ◽  
Stéphane DECHAMBRE ◽  
Christine SEMPOUX ◽  
Anne M. SMITH ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Contrast Agents ◽  
Molecular Mass ◽  
Hepatic Fibrosis ◽  
Mean Transit Time ◽  
Distribution Volume ◽  
High Molecular Mass ◽  
Permeability Changes ◽  
Molecular Masses ◽  
The Mean

Interstitial collagen formation and transformation of the fenestrated hepatic sinusoids into continuous capillaries are major ultrastructural changes that occur in liver cirrhosis and fibrosis. These modifications lead to progressive restriction of blood–liver exchanges. The purpose of our study was to evaluate the permeability changes in a model of hepatic fibrosis by using dynamic computed tomography (CT) enhanced with contrast agents of different molecular masses. Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass contrast agent (iobitridol) and an experimental high-molecular-mass agent (P840) in normal control rabbits and in rabbits with hepatic fibrosis. Hepatic, aortic and portal venous time–density curves were fitted with a dual-input one-compartmental model to calculate the hepatic mean transit time and distribution volume of the contrast agents. In the rabbits with liver fibrosis, the mean transit time of the high-molecular-mass agent was shorter than that of the low-molecular-mass agent (10.0±1.8s and 12.0±1.2s respectively; P<0.05). The distribution volume accessible to the high-molecular-mass agent was also smaller (22.2±4.8% compared with 32.0±6.7%; P<0.01). In the normal rabbits, the mean transit times of the high- and low-molecular-mass agents did not differ significantly, and nor did their distribution volumes. Our results demonstrate decreased sinusoidal permeability for the high-molecular-mass agent P840 in a model of hepatic fibrosis. Non-invasive assessment of permeability changes in liver fibrosis can be performed with dynamic CT and contrast agents of different molecular masses.

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