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عضویت

جستجوی مقالات مرتبط با کلیدواژه "liver fibrosis" در نشریات گروه "پزشکی"

  • Wenjing Liao, Fang Wu, Zhiyuan Hao, Jinglei Wu, Chenfei Liu, Min Wu, Xiaoman Zhou, Mingze Sun, Yuwei Liu *, Meng Fang
    Objective (s)

    Liver fibrosis (LF) is a critical stage in chronic liver disease progression, and effective therapeutic drugs are currently lacking. Tanshinone IIA (Tan IIA), a monomer extracted from Salvia miltiorrhiza, shows potential in treating LF. This research aims to discuss the antifibrotic efficacy and underlying pharmacological mechanism of Tan IIA. 

    Materials and Methods

    The in vivo model was induced with CCl4 to form a LF model in mice, and the in vitro model was induced by TGF-β1 in LX-2 and HSC-T6 cells. Liver pathology was characterized by HE, Masson, and Sirius red staining, and serum levels of ALT, AST, LDH, and γ-GT were examined. Cell viability and proliferation were detected by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution was detected by flow cytometry. The protein levels of p-ERK, cyclin D1, CDK4, and p-Smad3L were assessed through Western blot, immunohistochemistry, or immunofluorescence assays.

    Results

    Tan IIA markedly decreased serum levels of ALT, AST, LDH, and γ‐GT. Collagen I and α-SMA were reduced, as shown by in vitro and in vivo models. Moreover, while arresting HSCs in the G1 phase was increased, Tan II A markedly inhibited cell viability and colony formation. Mechanistically, Tan IIA decreased the expression of p-ERK, cyclin D1, CDK4, and p-Smad3L proteins in TGF-β1-activated cells and CCl4-induced mice.

    Conclusion

    Tan IIA may improve LF by regulating the signaling axis of ERK/cyclin D1/p-Smad3L, thereby blocking activated HSCs in the G1 phase and inhibiting their proliferation.

    Keywords: ERK, Cyclin D1, P-Smad3l - Signaling, Hepatic Stellate Cells, Liver Fibrosis, Tanshinone IIA, TGF-Β1
  • Azam Khedri, Mohammadreza Roshanazadeh, Mahdi Hatami, Arash Sanaei, Sahar Saki, Samaneh Salehipour Bavarsad *
    Background

    Hepatic fibrosis is a biological response characterized by the accumulation of extracellular matrix (ECM) during the wound healing process. Hepatic stellate cells (HSCs) play a pivotal role in fibrogenesis, transitioning from quiescent to myofibroblast cell types and leading to excessive ECM production. Platelet-derived growth factor (PDGF), a potent mitogen, is produced by activated HSCs, stimulating cell proliferation and migration.

    Objectives

    This study aims to analyze the impact of Wharton's jelly mesenchymal stem cell (WJ-MSC)-derived exosomes on HSC activation induced by PDGF during liver fibrosis.

    Methods

    Hepatic stellate cells-T6 cells were treated with PDGF-BB for 24 hours to induce activation, followed by treatment with varying concentrations of WJ-MSC-derived exosomes (0, 25, and 50 μg/mL) for another 24 hours. The effects of exosome treatment on HSC activation were evaluated through flow cytometry, differentiation assays, dynamic light scattering (DLS), transmission electron microscopy (TEM), RT-PCR, and western blot analysis.

    Results

    Our study yields promising results, highlighting the potential therapeutic effects of WJ-MSC-derived exosomes on liver fibrosis. The dose-dependent decrease in fibrotic markers such as α-SMA, COLA1, and phosphorylated AKT protein in PDGFBB- treated HSC-T6 cells suggests that WJ-MSC exosomes exert an anti-fibrotic effect by inhibiting HSC activation.

    Conclusions

    These findings suggest that exosomes derived from WJ-MSCs hold therapeutic promise for liver fibrosis treatment by targeting key pathways involved in HSC activation and fibrogenesis. Further investigation into the underlying mechanisms of this anti-fibrotic effect and the potential clinical applications of WJ-MSC-derived exosomes in liver fibrosis management is warranted.

    Keywords: PDGF-BB, P-AKT, WJ-Mscs, Exosome, Liver Fibrosis
  • Reyhane Ebrahimi, Abbas Sahebghadam Lotfi*
    Introduction

    Transforming growth factor (TGF)-β1 is crucial in developing liver fibrosis. Curcumin has been shown to effectively halt the advancement of liver fibrosis by inhibiting the TGF-β1/Smad signaling pathway. Nevertheless, curcumin's impact on liver fibrosis regression remains unclear. This study explored the involvement of curcumin and TGF-β1 in the regression of liver fibrosis.

    Methods

    An experimental male C57BL/6 mice model included  6 treatment groups. The treatment groups were injected with carbon tetrachloride (CCl4) for 4 and 6 weeks to induce liver fibrosis, negative controls were injected with olive oil. After cessation of injection, 2 of the treatment groups were given curcumin for 2 weeks. TGF-β1 expression in liver cells was analyzed by real-time PCR assay. ELISA analyzed hydroxyproline liver tissue levels. Values of p<0.05 were regarded as statistically significant.

    Results

    CCl4 injection induced liver fibrosis and significantly increased TGF-β1  expression and hydroxyproline levels in tissues. Curcumin administration decreased the expression of TGF-β1 and hydroxyproline levels in the liver and accelerated the regression of liver fibrosis.

    Conclusion

    Curcumin accelerates regression of liver fibrosis, likely through decreasing TGF-β1 expression in the liver.
    Keywords: Liver fibrosis, Carbon tetrachloride, Curcumin, TGF-β1, Hydroxyproline.

    Keywords: Liver Fibrosis, Carbon Tetrachloride, Curcumin, TGF-Β1, Hydroxyproline
  • پیمان الماسی نژاد، امین گلاب پور *
    مقدمه

     برای تشخیص کبد چرب غیرالکلی معمولا از آزمایش فیبرواسکن استفاده می شود که هزینه بالایی دارد. همچنین، آزمایشات کم هزینه مانند اندازه گیری آنزپم های کبدی یا آزمایشات هماتولوژی نمی توانند کبد چرب را به طور قطعی تشخیص دهند و فقط به عنوان ابزارهای اولیه در تشخیص کبد چرب به کار می روند.

    مواد و روش ها

     در این پژوهش، یک مدل یادگیری ماشین برای تشخیص کبد چرب با استفاده از اطلاعات دموگرافیک، آنزیم های کبدی و آزمایشات هماتولوژی ارایه گردید. برای این کار، داده ها از پرونده 1078 مراجعه کننده به بیمارستان امام رضا (ع) سال های 1397 تا 1402 استخراج شده است که شامل 25 متغیر وابسته می باشد. پس از پیش پردازش، اطلاعات به 531 پرونده کاهش یافت. برای جایگزینی داده های گمشده از الگوریتم بهینه سازی ذرات چندهدفه استفاده شد. پس از پیش پردازش، الگوریتم ماشین بردار پشتیبان بر روی این داده ها اجرا گردید. در نهایت، عملکرد الگوریتم پیشنهادی با الگوریتم های مشابه مقایسه و ارزیابی شد.

    نتایج

     در مرحله پیش پردازش، رکوردهایی که بیش از 20 درصد داده های گمشده داشتند حذف شدند و مابقی رکوردها جایگزینی شدند. سپس داده ها به دو مجموعه آموزش و تست با نسبت 70-30 تقسیم گردید. الگوریتم ماشین بردار پشتیبان با کرنل شعاعی بر روی داده های آموزشی اجرا شد و میزان حساسیت، ویژگی و صحت برای داده های آموزشی به ترتیب 24/96%، 86/90% و 55/93% حاصل گردید و برای داده های تست 80%، 22/77% و 62/78% به دست آمد. همچنین، در این پژوهش نشان داده شد که الگوریتم ماشین بردار پشتیبان پیشنهادی نسبت به شش الگوریتم مشابه عملکرد بهتری دارد.

    نتیجه گیری

     در این پژوهش نشان داده شده است که با استفاده از الگوریتم های یادگیری ماشین، می توان کبد چرب غیر الکی را با هزینه پایین تری تشخیص داد.

    کلید واژگان: یادگیری ماشین, فیروز کبدی, پیش بینی
    Peyman Almasi Nejad, Amin Golabpour *
    Introduction

    The diagnosis of NAFLD typically involves the use of the FibroScan test, which can be costly. More affordable options, like liver enzyme and hematology tests, cannot diagnose fatty liver disease; they only serve as preliminary tools for its diagnosis.

    Methods

    In this study, a machine-learning model was developed to diagnose fatty liver disease using demographic information, liver enzymes, and hematology tests. Data was extracted from the records of 1078 patients who visited Haj Marafi Hospital between 2018 and 2023, encompassing 25 dependent variables. After preprocessing, the data was reduced to 531 records. A multi-objective particle swarm optimization algorithm was used to impute missing data. Following preprocessing, a support vector machine (SVM) algorithm was applied to the data, and the performance of the proposed algorithm was compared and evaluated against similar algorithms.

    Results

    During preprocessing, records with more than 20% missing data were removed, and the remaining data were imputed. The data was then divided into training and testing sets (70-30 split). The radial basis function (RBF) SVM was applied to the training data, resulting in sensitivity, specificity, and accuracy of 96.24%, 90.86%, and 93.55%, respectively. For the test data, these rates were 80%, 77.22%, and 78.62%.

    Conclusion

    This study demonstrated that machine learning algorithms can diagnose NAFLD more cost-effectively.

    Keywords: Machine Learning, Liver Fibrosis, Prediction, Support Vector Machine
  • Sayed Mohammad Hosseeini, Mohammad Jafari, Marzieh Tahmasebi, Payman Adibi

    Non‑alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis (accumulation of fat in the liver to over 5% of its weight) in the absence of secondary causes of fat accumulation in the liver such as excessive alcohol use. NAFLD is divided into two types: non‑alcoholic fatty liver (NAFL) and non‑alcoholic steatohepatitis (NASH). Therefore, in this clinical guideline, we sought to determine general and important policies for this disease and modify its managment approaches. We adapted this guideline for the management of NAFLD in Isfahan Province. This guideline was developed by clinical appraisal and review of the evidence, available clinical guidelines, and in consultation with members of the Isfahan Chamber of the Iranian Association of Gastroenterology and Hepatology. Biopsy is recommended as the most reliable method (gold standard) to diagnose steatohepatitis and fibrosis in patients with NAFLD. NAFLD fibrosis score (NFS) and fibrosis‑4 (FIB‑4) are recommended as the test with the highest predictive value for advanced fibrosis in patients with NAFLD compared to other serologic tests. Among the noninvasive methods used to assess liver fibrosis, transient elastography (TE) is preferable to other methods.

    Keywords: Clinical Practice Guideline, Fatty Liver, Guideline, Liver Fibrosis, NAFL, NAFLD, NASH, Non‑Alcoholic Fatty Liver Disease, Non‑Alcoholic Fatty Liver, Non‑Alcoholic Steatohepatitis
  • Marjan Rangchi*, Abbas Sahebghadam Lotfi, Sarah Ali Hosseinzadeh
    Introduction

    Liver diseases are a significant global health burden, causing roughly two million deaths annually. Liver Fibrosis, characterized by excessive extracellular matrix accumulation, is a major contributor to morbidity and mortality. Liver transplantation remains the gold standard for severe Fibrosis, but limitations exist. Cell therapy using Mesenchymal Stem Cells offers a promising alternative. Hepatocyte-like Cells derived from human adipose tissue Mesenchymal Stem Cells are particularly attractive due to their potential for liver regeneration. This study aimed to compare the effectiveness of Mesenchymal stem cells and Hepatocyte-like cells in treating CCl4-induced Liver Fibrosis in immunosuppressed mice.

    Methods

    Twenty C57BL/6 mice were divided into four groups: (1) control, (2) Fibrotic/untreated, (3 Mesenchymal stem cell-treated, (4) Hepatocyte-like cell-treated. Fibrosis was induced in groups 2-4 using intraperitoneal CCl4 injection in immunosuppressed (cyclosporine A) mice. Mesenchymal Stem Cells and Hepatocyte-like Cells were transplanted via tail vein injection in groups 3 and 4, respectively. Liver function tests were measured in all groups.

    Results

    Both Mesenchymal Stem Cells and Hepatocyte-like Cells treatment improved liver function as evidenced by histopathology and biochemical analyses. In the Fibrotic group, Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase, and total bilirubin levels were significantly elevated, while Albumin levels decreased compared to the control group. Following treatment, these parameters significantly improved (p < 0.05) in both treatment groups, suggesting partial regression of Fibrosis.

    Conclusion

    Our findings suggest that both Hepatocyte-like Cells and Mesenchymal Stem Cells have therapeutic potential for moderating Liver Fibrosis regression. However, Mesenchymal Stem Cells therapy may be more cost-effective and time-efficient.

    Keywords: Liver Fibrosis, Mesenchymal Stem Cell, Hepatocyte-Like Cell, Cell Therapy
  • النا لک، اسکندر حاجیانی، جلال سیاح، زینب حسین پور، علیرضا صداقت*
    زمینه و هدف

    فیبروز کبدی مرحله نهایی بیماری مزمن کبدی است. دیابت با ریسک بالای فیبروز کبدی در بیماران کبد چرب غیرالکلی همراه است. همراهی پره دیابت و فیبروز کبدی در مطالعات قبلی چالش انگیز بوده است. هدف این مطالعه مقایسه فیبروز کبدی در بیماران مبتلا به دیابت و پره دیابت بود.

    روش بررسی

    مطالعه حاضر یک مطالعه توصیفی-مقطعی بود که بر روی مبتلایان به دیابت و پره دیابت، مراجعه کننده به بیمارستان امام خمینی اهواز از فروردین تا اسفند1401 انجام گردید. فیبروز کبد با الاستوگرافی اندازه گیری شد. ارتباط بین فیبروز کبدی و سن، جنس، BMI، AST، ALT، ALKP، Bilirubin و نوع درمان در دو گروه بررسی شد.

    یافته ها

    در این مطالعه 53 نفر (9/63%) مبتلا به دیابت و 30 نفر (1/36%) مبتلا به پره دیابت بودند. 47 نفر مرد (6/56%) و 36 نفر زن (4/43%) بودند. میانگین سن افراد شرکت کننده در پژوهش 06/49 سال بود. بین میانگین شدت فیبروز کبدی در بیماران دیابتی و پره دیابتی اختلاف معنادار وجود داشت. میانگین شدت فیبروز کبدی در افراد دیابتی 29/11 و در افراد پره دیابتی10/9 بود. بین فراوانی درجه فیبروز کبدی در بیماران دیابتی و پره دیابتی اختلاف معنادار وجود داشت (044/0=P). درجه فیبروز کبدی در تمامی سطوح به جز در گروه با فیبروز خفیف یا بدون فیبروز     (F0-F1) در افراد دیابتی بیشتر از پره دیابتی بود. در بیماران دیابتی بین FBS و فیبروز کبدی ارتباط معنادار مشاهده شد (001/0=P).

    نتیجه گیری

    شدت فیبروز کبدی در بیماران دیابتی بیشتر از بیماران پره دیابتیک بود. پره دیابت نیز با ریسک افزایش یافته فیبروز کبدی همراه بود.

    کلید واژگان: دیابت, فیبروز کبدی, پره دیابت
    Elena Lak, Eskandar Hajiani, Jalal Sayyah, Zeynab Hosseinpour, Alireza Sedaghat*
    Background

    Diabetes is known to be linked with a high risk of liver stiffness in non-alcoholic fatty liver patients. Previous studies have faced challenges in examining the association between prediabetes and liver stiffness. This study aimed to compare liver fibrosis in diabetes and prediabetes patients.

    Methods

    This cross-sectional descriptive study was conducted on patients with diabetes and prediabetes who were referred to Imam Khomeini Hospital in Ahvaz from March 2022 to March 2023. The study aimed to clear the relationship between liver stiffness and age, gender, BMI, AST, ALT, ALKP, Bilirubin, and the type of treatment. The normality of quantitative variables was checked using the Kolmogorov-Smirnov test. The chi-square test examined two qualitative variables with more than two levels.

    Results

    Out of the total participants, 53 people (63.9%) had diabetes, while 30 people (36.1%) had prediabetes. There was a significant difference between the mean severity of liver fibrosis in diabetic and pre-diabetic patients (P=0.014). The frequency of liver stiffness in all levels except in the group with mild or no fibrosis (F0-F1) was higher in diabetic than pre-diabetic patients. In both diabetes and prediabetes groups, there was no significant relationship between gender, age, BMI, ALT, and ALKP with liver fibrosis. However, there was a significant direct relationship between HbA1C% and liver fibrosis (P≥0.003) in both groups. In diabetic patients, a significant relationship between FBS and liver fibrosis was observed (P=0.001). In pre-diabetic patients, significant direct relationship was seen between the severity of liver fibrosis and AST levels (P=0.026).

    Conclusion

    Diabetic patients showed a higher severity of liver fibrosis compared to pre-diabetic patients. No statistically significant relationship was seen between liver fibrosis and age, sex, body mass index, ALT, and ALKP in both groups. Additionally, both diabetes and prediabetes groups showed significant relationship between liver fibrosis and HbA1C (P≥0.003). Prediabetes was also found to be associated with an elevated risk of liver fibrosis.

    Keywords: Diabetes, Liver Fibrosis, Prediabetes
  • Kamran Bagheri Lankarani, Seyed Ali Hosseini, Alireza Moaref, Hajar Khazraei, Seyed Vahid Hosseini, Abdulrazzaq Kalaf Hassan
    Background

    Although bariatric surgery has been introduced as a therapeutic option for patients with obesity, there is still debate on the choice of procedure.

    Objectives

    This study aimed to compare two types of bariatric surgeries in patients with obesity: Sleeve gastrectomy (SG) and single anastomosis sleeve ileal (SASI) bypass.

    Methods

    This observational prospective study compares patients with obesity who received either of the two types of bariatric surgeries at Ghadir or Shahid Faghihi hospitals in Shiraz from October 2019 to November 2020. Metabolic profiles, shear wave liver elastography (fibroscan), and cardiac evaluations (echocardiography) were performed at baseline and then seven to eleven months after the surgery.

    Results

    Forty-five patients with obesity who had undergone SG and SASI bypass entered this study. Fasting plasma glucose (FPG) and triglycerides (TG) decreased during the follow-up in both groups (P = 0.032, P < 0.001, respectively). The fibrosis score decreased significantly from 6.45 (4.55) before surgery to 5.40 (3.60) after surgery, and the cardiac ejection fraction increased significantly from 61.5% (12.5%) before surgery to 65.0% (8.5%) after surgery following the SASI bypass compared to the SG (P = 0.034, P = 0.008, respectively).

    Conclusions

    Despite the lack of difference in weight reduction, SASI bypass, compared to sleeve gastrectomy, may result in a more rapid improvement in cardiac function and liver fibrosis.

    Keywords: Sleeve Gastrectomy, SASI Bypass, Obesity, Metabolic Syndrome, Liver Fibrosis
  • محمدرضا فرزانه فر، مریم میری، فریماه نقیبیان، فروزان عامری زاده، معصومه سالاری*

    سندرم شوگرن اولیه یک بیماری خودایمنی سیستمیک است که شامل طیف گسترده ای از تظاهرات از جمله درگیری غدد برون ریز و علائم خارج غده ای است. این گزارش موردی به شرح حال زنی 26 ساله که با آسیت و ادم محیطی مراجعه کرده و سابقه پزشکی قبلی یا مصرف اخیر دارو نداشته است. آزمایشات اولیه لکوپنی، کم خونی، ترومبوسیتوپنی و عملکرد طبیعی کبد و کلیه را نشان داد. تجزیه و تحلیل مایع آسیت نشان داد درگیری کبد و تصویربرداری فیبروز قابل توجهی را در کبد نشان داد. آزمایش های آزمایشگاهی اضافی آنتی بادی های ضد هسته ای مثبت (ANA)، آنتی ژن A مرتبط با سندرم شوگرن (SS-A) و آنتی ژن B (SS-B) مربوط به سندرم شوگرن را نشان دادند و بیوپسی غدد بزاقی جزئی تشخیص را تایید کرد. سندرم شوگرن. بیمار با پردنیزولون، هیدروکسی کلروکین و مایکوفنولات موفتیل تحت درمان قرار گرفت که منجر به کاهش آسیت و ادم و بهبود سیتوپنی شد. این گزارش به اهمیت توجه به سندرم شوگرن در بیماران مبتلا به فیبروز کبدی و آسیت غیرقابل توضیح اشاره می کند.

    کلید واژگان: آسیت, بیماری خودایمنی, فیبروز کبدی, سندرم شوگرن
    Mohammadreza Farzaneh Far, Maryam Miri, Farimah Naghibian, Forouzan Amerizadeh, Masoumeh Salari*

    Primary Sjogren's syndrome is a systemic autoimmune disease that encompasses a wide range of manifestations, including exocrine gland involvement and extra-glandular symptoms. This case report deals with the history of a 26-year-old woman presented with ascites and peripheral edema and without any medical history or recent drug use. Initial tests demonstrated leukopenia, anemia, and thrombocytopenia, as well as normal liver and kidney function.  Ascitic fluid analysis A indicated liver involvement, and imaging displayed significant fibrosis in the liver. Additional laboratory tests showed positive antinuclear antibodies (ANA), anti-Sjögren's syndrome-related antigen A (SS-A), and anti-Sjögren's syndrome-related antigen B (SS-B) antibodies. Moreover, a minor salivary gland biopsy confirmed the diagnosis of Sjogren's syndrome. The patient was treated with prednisolone, hydroxychloroquine, and mycophenolate mofetil, which led to the reduction of ascites and edema and the improvement of cytopenia. This report highlighted the importance of considering Sjogren's syndrome in patients with liver fibrosis and unexplained ascites.

    Keywords: Ascites, Autoimmune Disease, Liver Fibrosis, Sjogren's Syndrome
  • Sara Ali Hosseinzadeh, Abbas Sahebghadam Lotfi, Nahid Davoodian, Sareh Arjmand, Marjan Rangchi, Fatemeh Mashhadiabbas
    Aim

    The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis.

    Background

    For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system.

    Methods

    Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice’s tail vein. Fourteen days’ post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson’s trichrome (MT) staining.

    Results

    Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT.

    Conclusion

    These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.

    Keywords: Liver Fibrosis, Adipose Tissue-Derived Mesenchymal Stem Cells, Alpha-1 Antitrypsin, Lentiviral Vectors, Carbon Tetrachloride
  • مجتبی رشیدی، مریم چراغ زاده، الهام شاکریان، عماد مطور، هستی بهشتی نسب، سمانه صالحی پور باورصاد*
    مقدمه

    بیماری فیبروز کبدی اغلب به فعال شدن سلول های ستاره ای کبد (Hepatic stellate cells) HSC و تشکیل بیش از حد زخم در کبد نسبت داده می شود. ایزورامنتین با مهار بیان ژن های فیبروژنیک ناشی از (Transforming growth factor beta) TGF-β1، در برابر فیبروز کبدی اثر محافظتی دارد. در این مطالعه، نقش ایزورامنتین بر میزان بیان فاکتورهای فیبروز کبدی و سطح (Reactive oxygen species) ROS در سلول های ستاره ای کبد مورد بررسی قرار گرفت.

    روش ها

    ابتدا سلول ها تا رسیدن به تراکم مناسب در محیط کشت DMEM همراه با 10 درصد از (Fetal Bovine Serum) FBS کشت داده شدند و با غلظت های 75 و 100 میکرومولار از ایزورامنتین به مدت 24 ساعت تیمار شدند، سپس میزان بیان ژن هایα-SMA ، Collagen1α ، NOX1، NOX2 و نیز سطح ROS برای ارزیابی فیبروز کبدی مورد سنجش قرار گرفت.

    یافته ها

    نتایج نشان داد که میزان بیان ژن هایα-SMA ، Collagen1α، NOX1، NOX2 و نیز سطح ROS در غلظت ng/m2 از TGF-β1 نسبت به گروه شاهد، افزایش معنی داری پیدا کرد. همچنین در حضور غلظت های 75 و 100 میکرومولار ایزورامنتین بیان این ژن ها و نیز سطح ROS نسبت به گروه فیبروز به صورت معنی داری کاهش یافت.

    نتیجه گیری

    TGF-β با افزایش بیان ژن های درگیر در پیشرفت بیماری فیبروز کبدی و نیز افزایش سطح ROS یافت افزایش تولید ماتریکس خارج سلولی از جمله Collagen1α می شود. ایزورامنتین باعث کاهش بیان ژن های درگیر در پیشرفت فیبروز کبدی می شود. در نتیجه می تواند از پیشرفت فیبروز کبدی جلوگیری کند.

    کلید واژگان: فیبروزکبدی, ایزورامنتین (3-متیل کوئرستین), TGF-Β1, NADPH اکسیداز, گونه های فعال اکسیژن
    Mojtaba Rashidi, Maryam Cheraghzadeh, Elham Shakerian, Emad Matour, Hasti Beheshti Nasab, Samaneh Salehipour Bavarsad *
    Background

    Liver fibrosis disease is often attributed to the activation of Hepatic Stellate Cells (HSC) and excessive scarring in the liver. Isoramantin has a protective effect against liver fibrosis by inhibiting the expression of fibrogenic genes caused by Transforming growth factor beta (TGF-β1). In this research, the role of Isorhamnetin in inhibiting the activation of liver stellate cells has been investigated.

    Methods

    First, the cells were cultured in DMEM culture medium with 10% of Fetal Bovine Serum (FBS) until reaching the appropriate density, and were treated with 75, 100 μM of Isorhamnetin for 24 hours, then the expression levels of NADPH Oxidase (NOX1, NOX2), Collagen1α, alpha-smooth muscle actin (α-SMA) and Reactive oxygen species (ROS) levels were measured to evaluate liver fibrosis.

    Findings

    The results showed that the expression level of NOX1, NOX2, Collagen1α, and α-SMA genes and the level of ROS in the concentration of 2ng/m of TGF-β increased significantly compared to the control group. Also, in the presence of 75 and 100 μM Isorhamnetin, the expression of these genes and the level of ROS decreased significantly compared to the fibrosis group.

    Conclusion

    TGF-β increases the expression of genes involved in the progression of liver fibrosis and increases the level of ROS, which increases the production of extracellular matrix, including collagen 1α. Isorhamnetin reduces the expression of genes involved in the development of liver fibrosis. Thus, it can prevent the development of liver fibrosis.

    Keywords: Liver Fibrosis, Isorhamnetin (3-Methylquercetin), Transforming Growth Factor Beta, NADPH Oxidase, Reactive Oxygen Species
  • Menglin Yao, Ting Wang, Tianpeng Liu, Qixin Zhao, Hongping Shen, Qin Sun *
    Background

     Macrophages play a significant role in both the development and regression of liver fibrosis, engaging in related pro-inflammatory and anti-inflammatory processes. In recent years, an increasing number of studies have elucidated the mechanisms by which macrophages influence liver fibrosis.

    Objectives

     This bibliometric analysis aims to investigate the research trends in liver fibrosis regulation by macrophages through a systematic literature review.

    Methods

     We conducted a search for literature, including research articles and reviews, using the keywords 'liver fibrosis and macrophages' and 'liver cirrhosis and macrophages' in the Web of Science database, covering the period from 2007 to 2023. We retrieved and analyzed publications on liver fibrosis mediated by macrophages from the Web of Science Core Collection database on October 8, 2023. Visualization analysis was performed using CreateSpace (version 6.1.R6), VOSviewer (version 1.6.19), and Scimago Graphica (version 1.0.34.0).

    Results

     We identified a total of 1732 records in the WoSCC, of which 1664 papers were ultimately included in our analysis. China emerged as the country with the most significant number of publications, while Germany and the University of California San Diego stood out for their influence, with centralities of 0.41 and 0.14, respectively. Frank Tacke was identified as the most prolific author, contributing 49 papers. Hepatology was the journal with the highest number of publications and citations. The most frequently mentioned keywords in this field were liver fibrosis, expression, hepatic stellate cells, activation, inflammation, and macrophages.

    Conclusions

     The study of macrophage-mediated liver fibrosis, particularly the mechanisms regulating the heterogeneity of hepatic macrophages, is a mature and promising research area. Macrophage-based therapies for liver fibrosis are anticipated to be crucial topics in the future. Bibliometric analysis offers valuable insights for future basic research directions and clinical practice.

    Keywords: Liver Fibrosis, Macrophages, Bibliometrics Analysis, CiteSpace, Vosviewer
  • Dun-Wei Yao, Hai-Xing Jiang, Shan-Yu Qin *
    Background

    This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis.

    Methods

    The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated.

    Results

    Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0 - S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94).

    Conclusions

    There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.

    Keywords: Endoscopic Ultrasound, Elastography, Liver Fibrosis, Strain Ratio, Liver Stiffness Measurement
  • Vladimir Vračarić, Božidar Dejanović *, Nebojsa Janjić, Milica Zirojević, Željka Savić, Olgica Latinović Bosnjak
    Background

     Hepatitis C and B virus infections significantly contribute to global chronic liver disease mortality.

    Objectives

     This study explores the role of serum markers (AST/ALT ratio, APRI Score, FIB-4 Score, and Forns index) in non-invasively assessing liver damage in patients with chronic hepatitis C and B.

    Methods

     In this single-center, retrospective, observational study, we analyzed data from 327 patients to establish correlations between serological markers and fibrosis grade using Spearman's correlation. Receiver operator characteristic (ROC) analysis evaluated the ability of these markers to predict advanced fibrosis.

    Results

     In hepatitis B and C cohorts, all markers show significant positive correlations with liver fibrosis (P < 0.001). FIB-4 and the Forns index exhibit moderate correlation (Spearman’s rho 0.48), while AST/ALT and APRI score show mild correlation (Spearman’s rho 0.21 and 0.31). In hepatitis C, the Forns index (0.814) and FIB-4 (0.80) outperform other markers. In hepatitis B, Forns (AUC = 0.73), APRI (AUC = 0.68), and FIB-4 (AUC = 0.68) demonstrate significant predictive ability.

    Conclusions

     FIB-4 and the Forns index hold clinical significance as fibrosis biomarkers in the management of chronic viral hepatitis. FIB-4 is a universal marker, while the interpretation of the Forns index requires consideration of the etiology of chronic viral hepatitis.

    Keywords: Hepatitis B, Hepatitis C, Liver Fibrosis, Cirrhosis, APRI, FIB-4, Forns
  • Dun-Wei Yao, Hai-Xing Jiang, Shan-Yu Qin *
    Background

     This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis.

    Methods

     The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated.

    Results

     Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0 - S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94).

    Conclusions

     There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.

    Keywords: Endoscopic Ultrasound, Elastography, Liver Fibrosis, Strain Ratio, Liver Stiffness Measurement
  • Abazar Parsi, Eskandar Hajiani, Somayeh Sadani, Seid Jalal Hashemi, Seid Saeed Seyedian, Mehdi Alimadadi *, Reza Ghanbari
    Background

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world. Previous studies revealed that cholecystectomy may be considered a risk factor for the development of NAFLD. The aim of this study was to compare the amount of liver fibrosis, determined by elastography, between patients with NAFLD with and without a history of cholecystectomy.

    Methods

    In this descriptive-analytical cross-sectional study, 50 patients with NAFLD were divided into two groups: one with a history of cholecystectomy and the other without. No significant differences were found between these two groups in terms of age or sex distribution. Liver fibrosis was measured for all patients using an elastography imaging system. Subsequently, the data related to liver fibrosis, along with the demographic information of the patients, were statistically analyzed using SPSS software version 22.

    Results

    The mean elastography score in all patients was 10.66 ± 12.18 kPa (the elasticity scale ranging from 3.80 to 66.40 kPa). The group with a history of cholecystectomy had a significantly higher mean elastography score (13.39 ± 16.20 kPa) compared with the group without cholecystectomy (7.93 ± 4.99 kPa) (P = 0.02). Additionally, there was a significant positive correlation between body mass index (BMI) and the mean elastography score in the group of patients with a history of cholecystectomy.

    Conclusion

    The mean elastography score of patients with NAFLD with a history of cholecystectomy was approximately twice as high as that of non-cholecystectomy patients.

    Keywords: Non-alcoholic fatty liver disease, Liver fibrosis, Elastography, Cholecystectomy
  • Parisa Varjavand, Ardeshir Hesampour*
    Background

    Persistent liver damage contributes to the development of liver fibrosis, marked by an accumulation of extracellular matrix. Macrophages play a pivotal role in this process, with the CCL2-CCR2 and CX3CR1-CX3CL1 axes serving as key regulators of macrophage recruitment, liver infiltration, and differentiation. In this study, utilizing a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis, we aimed to investigate the impact of imatinib and bone marrow-derived mesenchymal stem cells (BM-MSCs) on the expression of these axis.

    Methods

    Sixteen Sprague-Dawley rats were divided into four groups: healthy, liver fibrosis, imatinib-recipient, and BM-MSC-recipient. Treatment effects were evaluated using histopathology and Sirus-red staining. Quantitative real-time PCR was employed to analyze changes in the expression of the genes CCL2, CCR2, CX3CL1, and CX3CR1.

    Results

    Histopathological assessments revealed the efficacy of imatinib and BM-MSCs in mitigating liver fibrosis. Our findings demonstrated a significant reduction in CCL2 and CCR2 expression in both imatinib and BM-MSCs treatment groups compared to the liver fibrosis group. Conversely, the gene expression of CX3CL1 and CX3CR1 increased in both therapeutic groups compared to the liver fibrosis groups.

    Conclusion

    The notable decrease in CCL2-CCR2 genes in both therapeutic groups suggests that BM-MSCs and imatinib may contribute to a decline in inflammatory macrophages within the liver. The lower CCL2-CCR2 expression in imatinib-recipient rats indicates better efficacy in modulating the recruitment of inflammatory macrophages. The elevated expression of CX3CL1 in BM-MSC-recipient rats suggests a greater impact on the polarization of LY6Chigh (inflammatory) to LY6Clow (anti-inflammatory) macrophages, warranting further investigation.

    Keywords: CCL2, CCR2, CX3CL1, CX3CR1, Liver fibrosis
  • لطف الله داودی، حسین جلالی، رویا پورمجیب، محمد عابدی سماکوش، طهورا موسوی*
    سابقه و هدف

    یکی از عوامل احتمالی ادامه عفونت هپاتیت B در بالغین همودیالیزی وجود هپاتیت B مخفی است. با توجه به این که احتمال وجود عفونت مخفی هپاتیت B در بین بیماران نقص ایمنی به ویژه همودیالیزی وجود دارد، هدف از این مطالعه بررسی میزان فراوانی هپاتیتB مخفی در بیماران دیالیزی شهرستان ساری بوده است.

    مواد و روش ها

    در این مطالعه توصیفی- مقطعی که در سال 1398 در شهر ساری انجام شد. خون گیری در بیماران دیالیزی، قبل از دیالیز انجام شد و سپس تست های سرولوژی با استفاده از کیت های مخصوص با روش الایزا از نظر HBs-Ab,HBs-Ag و HBV PCR,HBc-Ab انجام شد. تجزیه و تحلیل داده ها با استفاده از نرم افزار آماری SPSS انجام شد. برای ارتباط بین متغیرهای کیفی از آزمون Chi-Square استفاده شد. هم چنین برای مقایسه بین دو گروه از آزمون تی مستقل استفاده شد و مقدار 05/0P< به عنوان سطح معنی داری در نظر گرفته شد.

    یافته ها

    تعداد افراد مورد بررسی در این مطالعه 279 نفر بودند. آزمون مجذور کای نشان داد که تفاوت معنی داری بین دو گروه از لحاظ جنس وجود نداشت (0/05<P) ولی به طور معنی داری اکثر بیماران مورد مطالعه سابقه قبلی دیابت و فشارخون بالا داشتند (0/05>P). هم چنین نشان داده شد که رابطه معنی داری بین هپاتیت B مخفی و اطلاعات دموگرافیک مورد بررسی وجود ندارد (0/05<P). آزمون تی مستقل نشان داد که به طور معنی داری میانگین سنی افراد با هپاتیت B مخفی بالاتر از باقی بیماران دیالیزی است(0/030=P). از بین افراد بیمار، 9 نفر (3/23 درصد) (HBs Ag) مثبت داشتند، که 7 نفر تحت درمان بودند و دونفر نیاز به درمان نداشتند. با وجود دو دوره کامل واکسیناسیون 6 بیمار 2 درصد (با HBs Ag و HBs Ab) منفی گزارش شد که HBc Ab مثبت داشتند (0/71 درصد) 2 مورد از آن ها PCR مثبت بوده که به عنوان هپاتیت نهفته واقعی معرفی شدند و 4 نفر دیگر به عنوان هپاتیت بهبود یافته قدیمی ثبت شدند.

    استنتاج

    طبق ارزیابی ها می توان دریافت که در افراد ESRD (End-Stage Renal Disease) بررسی فاکتور HBs Ag به تنهایی کافی نیست و حتما باید HBc Ab نیز بررسی شود و در صورت مثبت بودن نمونه های بیماران توسط PCR ارزیابی شوند.

    کلید واژگان: همو-دیالیز, هپاتیت B مخفی, فیبروز کبدی, نقص ایمنی
    Lotfollah Davood, Hossein Jalali, Roya Poormojib, Mohammad Abedi Samakoosh, Tahoora Mousavi*

    Background and

    purpose

    One of the possible factors for the continuation of hepatitis B infection in hemodialysis adults is the presence of hidden hepatitis B. Considering the risk of occult hepatitis B infection in people with immunodeficiency disorders, especially hemodialysis patients, the aim of this study was to investigate the frequency of occult hepatitis B among dialysis patients in Sari.

    Materials and methods

    This cross-sectional descriptive research was conducted in Sari, 2018. Blood samples were taken from dialysis patients before dialysis. Then, HBV serology tests (HBs-Ab, HBs-Ag, HBV PCR, and HBc-Ab) were performed using ELISA method. Data analysis was done using SPSS V20. Chi-square test was used to find correlation between qualitative variables. Also, the differences were compared using independent t-test, and P<0.05 was considered significant.

    Results

    A total of 279 dialysis patients were investigated in this study. The chi-square test showed that there was no significant difference between the two groups in terms of gender (P>0.05), but significantly, the majority of the studied patients had a previous history of diabetes and high blood pressure (P<0.05). The findings revealed that there was no significant relationship between latent hepatitis B and demographic information (P>0.05). Independent t-test showed that the average age of people with latent hepatitis B was significantly higher than the rest of dialysis patients. (P=0.030). Of the patients, nine (3.23%) had positive HBs-Ag, of whom seven were under treatment and two did not need any treatment. Despite two complete series of vaccination against hepatitis B, six patients (2%) with negative HBs-Ag and HBs-Ab were reported to have positive HBc-Ab. Two cases of them (0.71%) were PCR positive, which were real latent hepatitis, and four others were recorded as old recovered hepatitis.

    Conclusion

    The findings suggested that HBs-Ag was a necessary but not sufficient factor in patients with End-Stage Renal Disease (ESRD); therefore, it was recommended to evaluate HBc-Ab and to test PCR for positive cases.

    Keywords: dialysis, occult hepatitis, liver fibrosis, immunodeficiency
  • سودابه حامدی شهرکی، فرشاد امیرخیزی، سهیل پورحیدر، عباس پیشدادیان*
    سابقه و هدف

    بیوپسی معیار استاندارد تشخیص فیبروز کبدی است، اما به دلیل تهاجمی بودن، خطر عوارض و خطاهای نمونه گیری، به طور گسترده برای پایش فیبروز کبد استفاده نمی شود. این مطالعه با هدف ارزیابی اهمیت بالینی چندین شاخص غیرتهاجمی در تشخیص بیماری و در پیش بینی فیبروز پیشرفته کبد درکودکان مبتلا به هپاتیت خودایمن(AIH) انجام شد.

    مواد و روش ها

    در این مطالعه مقطعی آینده نگر، برای 40 کودک مبتلا به AIH، شمارش کامل خون و آزمایش های عملکرد کبد انجام شد و شاخص های مشتق از آن ها محاسبه شد. تمامی بیماران مبتلا به AIH بر اساس بیوپسی کبد به دو گروه فاقد فیبروز/فیبروز خفیف و فیبروز متوسط/شدید (فیبروز پیشرفته) تقسیم شدند.

    یافته ها

    در بیماران مبتلا به AIH میزان شاخص نسبت آسپارتات آمینوترانسفراز به پلاکت (APRI) و شاخص فیبروز بر اساس چهار فاکتور (FIB-4)، افزایش معنی دار (0/001P<) و میزان شاخص نسبت نوتروفیل به لنفوسیت (NLR)، کاهش معنی دار (0/041P=) در مقایسه با افراد سالم داشت. در بیماران مبتلا به فیبروز پیشرفته، میزان بیلی روبین مستقیم (DBIL) و APRI به طور قابل توجه بیش تر و میزان آلبومین به طور قابل توجه کم تر در مقایسه با گروه فاقد فیبروز/فیبروز خفیف بود. تجزیه و تحلیل سطح زیر منحنی مشخصه عملکرد گیرنده (AUC) نشان داد که FIB-4 و APRI برای تشخیص بیماری AIH در کودکان و DBIL و APRI برای تشخیص فیبروز پیشرفته کبدی در کودکان مبتلا به AIH دارای ارزش بالینی هستند.

    استنتاج

    APRI می تواند به عنوان شاخص مرجع برای تشخیص بیماری AIH در کودکان و نیز پایش فیبروز کبدی در کودکان مبتلا به AIH مورد استفاده قرار گیرد.

    کلید واژگان: هپاتیت خودایمن, شاخص غیرتهاجمی, بیوپسی کبد, فیبروز کبد, APRI
    Soudabeh Hamedi-Shahraki, Farshad Amirkhizi, Soheil Pourheidar, Abbas Pishdadian*
    Background and purpose

    Biopsy is the standard criterion for the diagnosis of liver fibrosis, but it is not widely used for liver fibrosis monitoring due to its invasive nature, risk of complications, and sampling errors. This study aimed to evaluate the clinical significance of several noninvasive indices in diagnosis of the disease and in prediction of advanced liver fibrosis in children with autoimmune hepatitis (AIH).

    Materials and methods

    In a prospective cross-sectional study, in 40 children with AIH, complete blood count and liver function tests were performed and their derived indices were calculated. Based on liver biopsy, all patients with AIH were divided into two groups: absent/mild fibrosis and moderate/severe fibrosis (advanced fibrosis).

    Results

    In patients with AIH, aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) increased significantly (P<0.001) and neutrophil to lymphocyte ratio index (NLR) decreased significantly (P=0.041) compared to healthy individuals. In patients with advanced fibrosis, direct bilirubin (DBIL) and APRI levels were considerably higher and albumin levels were considerably lower compared to the absent/mild fibrosis group. Analysis of the area under the receiver operating characteristic curve (AUC) showed that FIB-4 and APRI have clinical value for the diagnosis of AIH in children while DBIL and APRI had clinical value in diagnosis of advanced liver fibrosis in these children.

    Conclusion

    APRI can be used as a reference index in diagnosis of AIH in children and to monitor liver fibrosis in children with autoimmune hepatitis.

    Keywords: autoimmune hepatitis, noninvasive index, liver biopsy, liver fibrosis, APRI
  • Rehab Fawzy Abdel-Rahman*, Hany M Fayed, Marwan A Mohamed, Alyaa F Hessin, Gihan F Asaad, Sahar S AbdelRahman, Abeer A Salama, Mahmoud S Arbid, Hanan A Ogaly
    Introduction

    Liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. The goal of this investigation was to look into the anti-fibrotic effect of apigenin (APG), an antioxidant found in various plants, versus thioacetamide (TAA)-triggered hepatic scarring in rats and the potential mechanisms behind it.

    Methods

    TAA was administered thrice weekly (100 mg/kg, i.p.) for two weeks to produce hepatic scarring. APG was administered after TAA for 14 days (5 or 10 mg/kg, orally). Thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated.

    Results

    TAA increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (FAK), hypoxia-inducible factor-1α (HIF-1α), and inflammatory cytokines, decreased interleukin-10 (IL-10), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and elevated serine-threonine protein kinase (AKT) expression. Furthermore, TAA increased hepatic contents of collagen I, connective tissue growth factor (CTGF), hydroxyproline, and alpha-smooth muscle actin. On the other hand, APG evaded these changes and mitigated the harmful effects of TAA in a dose-dependent way. Histopathological and immunohistochemical observations reinforced these biochemical outcomes.

    Conclusion

    APG can potentially alleviate liver fibrosis mediated via FAK and HIF1 inhibiting signaling pathways.

    Keywords: Transforming growth factor beta 1, Tumour necrosis factor alpha, Alpha-smooth muscle actin, Hydroxyproline, Liver fibrosis, Rats
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