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[EFFECT OF BLOOD MICROENVIRONMENT OF RATS WITH HEPATIC FIBROSIS ON DIFFERENTIATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS INTO HEPATOCYTES AND ITS MECHANISMS].

OBJECTIVE: To investigate the effect of blood microenvironment of rats with hepatic fibrosis on differentiation of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes and its mechanisms. METHODS: Eighteen male adult Sprague Dawley rats [weighing, (200±20) g] were used, liver fibrosis was induced in 12 rats by repeated intraperitoneal injections of thioacetamide. The serum was separated after successful model preparation, and the serum of 6 normal rats was collected. ELISA assay was used to detect the concentrations of epidermal growth factor (EGF), hepatocyte growth factor …

An Analysis of the Hypothalamic-Pituitary-Adrenal Axis Functions in Cirrhotic Rats in Response to Surgical Stress.

INTRODUCTION: The activation of hypothalamic-pituitary-adrenal (HPA) axis through severe diseases and stress courses leads to a rise in circ … d by the Ethics Committee of Tehran University of Medical Sciences in 2014, on 25 male Wistar rats. Thioacetamide was used for induction of cirrhosis in rats with new method of monitoring weekly changes of rats' weight which had 100% success in procedure and reduction in mortality rate. Laparotomy was performed on all of the rats during 9-12 in the morning with …

Dysregulation of bile acid signal transduction causes neurological dysfunction in cirrhosis rats.

BACKGROUND: The pathogenesis of hepatic encephalopathy (HE) remains unclear, and the classical theory of ammonia toxicity lacks sufficient justification. AIM: To investigate the potential of bile acids as intervention targets for HE. METHODS: This study employed 42 wild-type male SD rats weighing 200 ± 20 g. Using a random number table method, two rats were randomly selected to undergo common bile duct ligation (BDL). The remaining 40 rats were randomly assigned to four groups serving as controls: The vehicle + control diet (VC) group, the thioacetamide (TAA) group, the TAA + total bile acid…

BabaoDan cures hepatic encephalopathy by decreasing ammonia levels and alleviating inflammation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: BabaoDan (BBD) is a famous traditional Chinese formula frequently used in TCM clinics to eliminate jaundice and treat infectious viral hepatitis. This paper assesses BBD's preventive and therapeutic effects on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism of action. METHODS: CHE rat model was established by injection of carbon tetrachloride (CCl4) twice a week for a total of 9 weeks and then by injection of thioacetamide (TAA) to induce hepatic encephalopathy. AHE rat model was estab…

Brahma-Related Gene 1 Inhibition Prevents Liver Fibrosis and Cholangiocarcinoma by Attenuating Progenitor Expansion.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) is closely correlated with hepatic progenitor cell (HPC) expansion and liver fibrosis. Brahma-related gene 1 (Brg1), an enzymatic subunit of the switch/sucrose nonfermentable complex that is critical in stem cell maintenance and tumor promotion, is prominently up-regulated in both HPCs and iCCA; however, its role in this correlation remains undefined. APPROACH AND RESULTS: A retrospective cohort study indicated that high Brg1 expression suggests poor prognosis in patients with iCCA. In chronically injured livers induced by a 0.1% 3,5

Gas6 deficiency prevents liver inflammation, steatohepatitis, and fibrosis in mice.

The Gas6/Axl pathway has been increasingly implicated in regeneration and tissue repair and, recently, in the control of innate immunity. In liver, we have demonstrated that Gas6 and its receptor Axl are expressed in macrophages, progenitor cells, and myofibroblasts and that Gas6 deficiency reduced inflammation and myofibroblast activation, causing delayed liver repair in response to acute injury. All these data suggest a role of Gas6/Axl signaling in pathogenesis of chronic liver diseases. In the present study, we address the role of Gas6 in steatohepatitis and progression to liver fibrosis u

A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis.

ObjectiveThis meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models.MethodsA systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle's RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias.ResultsThis meta-analysis included 24 studies involving 440 animals with methodological quality scores

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… .: oral administration; TAA: thioacetamide; H&E: hematoxylin and eosin. … Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: impact on TGF-β/Smad3 and NF-κB signaling pathways . Toxicol. Mech. Methods 30 ( 8 ), 620 – 633 . 10.1080/15376516.2020.1801926 32718261 Hammerich L. Tacke F. ( 2023 ). …

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

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… In 2021, Wang et al. obtained a transcription profile by single-cell RNAseq (sc-RNAseq) in fibrotic and cirrhotic compared to healthy human livers, using an in vivo model of thioacetamide (TAA)- and bile duct ligation (BDL)-induced liver fibrosis in rat models [ 70 ]. … Moreover, the role of A6 was investigated in liver fibrosis using two mouse models: male mice on a choline-deficient, high-fat diet (CD-HFD) and thioacetamide (TAA). …

RAR-Related Orphan Receptor Gamma (ROR-γ) Mediates Epithelial-Mesenchymal Transition Of Hepatocytes During Hepatic Fibrosis.

The epithelial-mesenchymal transition (EMT) is involved in many different types of cellular behavior, including liver fibrosis. In this report, we studied a novel function of RAR-related orphan receptor gamma (ROR-γ) in hepatocyte EMT during liver fibrosis. To induce EMT in vitro, primary hepatocytes and FL83B cells were treated with TGF-β1. Expression of ROR-γ was analyzed by Western blot in the fibrotic mouse livers and human livers with cirrhosis. To verify the role of ROR-γ in hepatocyte EMT, we silenced ROR-γ in FL83B cells using a lentiviral short hairpin RNA (shRNA) vector. The therapeu

Arctiin Inhibits Inflammation, Fibrosis, and Tumor Cell Migration in Rats With Ehrlich Solid Carcinoma.

Background and objectivesESC or Ehrlich solid carcinoma is a type of tumor originating from a spontaneous mammary adenocarcinoma in mice. It is a highly aggressive and fast-growing carcinoma that can create a solid mass when inserted under the skin. Its solid, undifferentiated form makes it an ideal model for researching cancer biology, tumor immunology, and testing various anti-cancer treatments. Additionally, arctiin has multiple beneficial properties, such as anti-proliferative, anti-oxidative, anti-adipogenic, and anti-bacterial. This study aimed to explore the potential anti-cancer benefi

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… induced in rats via affecting inflammation, cell proliferation, and DNA polymerization Cureus Alatawi YF Alhablani MA Al-Rashidi FA Khubrani WS Alqaisi SA Hassan HM Al-Gayyar MM 15 2023 10.7759/cureus.43317 PMC10415854 37577271 20 Evaluating the anticancer activity of blocking TNF type 1 receptors in thioacetamide-induced …

Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?

Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypep

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… Hepatoprotective effects were also observed for saxagliptin in a rat model of hepatic injury induced by thioacetamide [ 117 ]. … Saxagliptin reduced the serum levels of the markers of hepatocellular injury and alpha-fetoprotein, diminished the histopathological changes induced by thioacetamide, and deferred the occurrence of hepatocellular carcinoma, possibly by suppressing Wnt/Hedgehog/Notch1 signaling. …

POEMS syndrome misdiagnosed as liver cirrhosis: a case report.

POEMS syndrome is a rare multisystem paraneoplastic disorder characterized by polyneuropathy and monoclonal plasma cell proliferation, often leading to delayed diagnoses due to variable clinical manifestations. A 62-year-old woman presented with persistent bilateral eyelid edema as the initial symptom and abdominal distension as the predominant complaint. She was misdiagnosed with liver cirrhosis and remained undiagnosed for 6 years. Multidisciplinary evaluation revealed monoclonal IgA λ protein, markedly elevated vascular endothelial growth factor, and neurophysiological evidence of periphera

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… Combination of systemic thioacetamide (TAA) injections and ethanol feeding accelerates hepatic fibrosis in C3H/he mice and is associated with intrahepatic up regulation of MMP-2, VEGF and ICAM-1 . J Hepatol . ( 2006 ) 45 : 370 – 6 . doi: 10.1016/j.jhep.2006.03.017 , 16780996 16. …

Оценка изменений в геморрологических переменных у пациентов с множественным склерозом.

Множественный склероз (MS) — нейродегенеративное состояние, обусловленное главным образом дисрегуляцией иммунной системы. Однако появляющиеся данные свидетельствуют о том, что дополнительные факторы, такие, как нейродегенерация, независимо от иммунных процессов, могут также способствовать патологии MS. С учетом значительного числа случаев гипоперизолирования головного мозга, наблюдавшихся у пациентов с церебральным кровотечением от раннего до продвинутого этапа заболевания, исследование гемореологии или револогии крови, которое включает изучение свойств кровотока крови и плазменных белковых со

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… health status and disability due to breathlessness in chronic obstructive pulmonary disease patients Clin Respir J 2021 15 11 1168 74 10.1111/crj.13423 34310080 Safapoor S et al Synthesis, ADMT prediction, and in vitro and in silico α-glucosidase inhibition evaluations of new quinoline– quinazolinone–thioacetamides …

Engineered mesenchymal stem cell-derived exosomes: A revolutionary approach to unlocking liver disease treatment.

Exosomes, a specific type of extracellular vesicle with diameters ranging from 30 to 150 nm, play a vital role in coordinating various physiological and pathological processes through direct cell-to-cell communication. These vesicles transport a diverse range of molecules, including proteins, mRNAs, miRNAs, and lipids, that originate from parent cells. Exosomes are released by nearly all cell types, including mesenchymal stem cells (MSCs), and possess significant potential due to their regenerative and immunomodulatory properties. In the context of liver disease treatment, these capabilities o

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… MSCs show promise in treating various forms of acute liver injury, including those caused by lipopolysaccharide (LPS), thioacetamide, ischemia-reperfusion (I/R), and radiation [ [113] , [114] , [115] , [116] , [117] , [118] ]. … Canine mesenchymal stem cells show antioxidant properties against thioacetamide‐induced liver injury in vitro and in vivo. Hepatol. Res. 2014;44(10):E206–E217. doi: 10.1111/hepr.12204. 115. Fu J., Zhang H., Zhuang Y., Liu H., Shi Q., Li D., et al. …

HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases.

Fibrosis is characterized by excessive deposition of the extracellular matrix and develops because of fibroblast differentiation during the process of inflammation. Various cytokines stimulate resident fibroblasts, which differentiate into myofibroblasts. Myofibroblasts actively synthesize an excessive amount of extracellular matrix, which indicates pathologic fibrosis. Although initial fibrosis is a physiologic response, the accumulated fibrous material causes failure of normal organ function. Cardiac fibrosis interferes with proper diastole, whereas pulmonary fibrosis results in chronic hypo

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… Valproate ameliorates thioacetamide-induced fibrosis by hepatic stellate cell inactivation Hum. Exp. Toxicol. 2015 34 44 55 10.1177/0960327114531992 24812151 40. Kee H.J. Sohn I.S. Nam K.I. Park J.E. Qian Y.R. Yin Z. Ahn Y. Jeong M.H. Bang Y.J. Kim N. …

The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.

Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular matrix (ECM) remodelling, myofibroblast differentiation and apoptosis, HSP 90 has been investigated as a key player in the pathogenesis of lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is the most common and deadly interstitial lung disease, due to the progressive distortion of lung parenchyma

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… The heat shock protein 90 inhibitor, 17-AAG, attenuates thioacetamide induced liver fibrosis in mice. Pharmacol Rep 2016; 68: 275–282. doi: 10.1016/j.pharep.2015.08.015 64. Datta R, Bansal T, Rana S, et al. …

Pleiotropic Effects of Modified Citrus Pectin.

Modified citrus pectin (MCP) has a low-molecular-weight degree of esterification to allow absorption from the small intestinal epithelium into the circulation. MCP produces pleiotropic effects, including but not limited to its antagonism of galectin-3, which have shown benefit in preclinical and clinical models. Regarding cancer, MCP modulates several rate-limiting steps of the metastatic cascade. MCP can also affect cancer cell resistance to chemotherapy. Regarding fibrotic diseases, MCP modulates many of the steps involved in the pathogenesis of aortic stenosis. MCP also reduces fibrosis to

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… Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease PLoS ONE 2013 8 e75361 10.1371/journal.pone.0075361 24130706 PMC3793988 110. Traber P.G. Zomer E. …

Липидированные мезофорные наночастицы, нагруженные тимокиноном, в качестве нового метода лечения аутоиммунного энцефаломиелита у крыс.

AIMS: Пересечение мозгового барьера (BBB) по-прежнему является серьезной проблемой для доставки терапевтических агентов в центральную нервную систему. Цель этого исследования состояла в том, чтобы оценить потенциал новых наноформуляционных силикатных силиканочастиц (MSN), покрытых липидным двуслойным слоем (LB), с тем чтобы повысить уровень доставки и потенциальное ремиелионирующее воздействие тимокинона (TQ). МЕТОДЫ: Составы характеризовались микроскопией передачи электронов и динамическим рассеиванием света для определения потенциала зета и размера частиц. Экспериментальная аутоиммунная энце

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… Thymoquinone improves Behavioral and Biochemical deficits in hepatic encephalopathy induced by thioacetamide in rats. Neurosci Lett. 2021;745(February):135617. 10.1016/J.NEULET.2020.135617. 54. Moyaho A, Eguibar JR, Diaz JL. …

15th Report on Carcinogens.

BACKGROUND: The Report on Carcinogens (RoC) is a congressionally mandated, science-based public health document that the National Toxicology … ; 2,3,7,8-Tetrachlorodibenzo-p-dioxin; Tetrachloroethylene; Tetrafluoroethylene; Tetranitromethane; Thioacetamide; 4,4'-Thiodianiline; Thiotepa; Thiourea; Thorium Dioxide (see Ionizing Radiation); Tobacco Smoke, Environmental (see Tobacco-Related Exposures); Tobacco, Smokeless (see Tobacco-Related Exposures); Tobacco Smoking (see Tobacco-Related Exposures); Tol …

Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.

Food antioxidant supplementation has been widely proposed for cancer prevention and adjuvant therapy due to the pleiotropic role of antioxidants. Herein, particular attention is given to recent clinical trials based on the use of dietary supplements in cancer patients, both as monotherapy and in combination with standard treatments, exploring both their potential benefits and risks. This review focuses on the efficacy of the most important food antioxidants, highlighting how their action may change depending on different factors such as cancer type, dose, timing of administration and antioxida