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This article considers the antifibrotic properties of pyrimidine derivatives of the drug Xymedon (compound (I)) and its conjugate with L-ascorbic acid (compound (II)) in an experimental rat model of fibrosis with a preventive administration scheme.Experimental fibrosis was induced in Wistar rats given carbon tetrachloride (5% oil solution, 0.2 mL/kg orally twice a week) in combination with ethanol (5% solution in drinking water, free access) against compounds (I) and (II), both administered preventively. Fibrotic changes in the liver were detected by Van Gieson’s staining. The effects of the studied compounds on the liver and clinical condition of rats were evaluated through serum biochemical parameters.The treatment of rats with compounds (I) and (II) reduced the number of fibrotic areas threefold, ameliorated hepatic steatosis and necrosis as compared to the control group, and improved blood biochemical parameters (ALT, AST, and LDH). Interestingly, compound (II) had a more pronounced effect.Therefore, pyrimidine derivatives of Xymedon and its conjugate with L-ascorbic acid showed an antifibrotic effect in our experimental rat model of fibrosis.

Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity. [ABSTRACT FROM AUTHOR]

Mineralocorticoid receptor antagonists have been successfully used for many years to treat patients with primary hyperaldosteronism, refractory arterial hypertension and chronic heart failure. The increased interest in this drug in recent years is due to new information about its antifibrotic and antiproliferative effects, both cardiac and extracardiac. The article also discusses the possibility of using spironolactone in patients with the new coronavirus infection SARS-CoV-2 (COVID-19).

Objectives: Vocal fold (VF) scarring and laryngeal stenosis are a significant clinical challenge. Excessive scar formation causes low voice quality or even life-threatening obstructions. Cytokines are thought to modulate multiple steps of the establishment of VF fibrosis, but there is no systematic report regarding their role in modulating VF fibrosis. This review aims to investigate the role of cytokines in modulating vocal fold fibrosis.Study Design: Literature review.Methods: This review searched for all relevant peer publications in English for the period 2009 to 2019 in the PubMed database using search terms: "laryngeal stenosis," "vocal fold scarring," and "cytokines." A thorough investigation of the methods and results of the reviewed studies was performed.Results: Comprehensive research in various studies, including analyses of prostaglandin E2 (PGE2), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), transforming growth factor-β3 (TGF-β3), and interleukin-10 (IL-10), supports cytokine therapy for VF scarring and laryngeal stenosis to some extent. A few clinical studies on this topic support the conclusion that HGF and bFGF can be selected as effective drugs, and no serious side effects were found.Conclusions: This review describes the potential of cytokines for modulating the process of VF fibrogenesis, although cytokines are still an unproven treatment method. As no ideal drugs exist, cytokines may be considered the candidate treatment for preventing VF fibrogenesis. Laryngoscope, 131:139-145, 2021. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is one of chronic liver diseases with high disability and mortality accompanying fibrosis, hepatocyte damage, and liver dysfunction. In this study, the hepatoprotective and the antifibrotic properties of lesimarin(lecithin - silymarin - Artemisia messerschmitiana Besser(AMB) extract complex at 11:3:6 ratio) on rat hepatic fibrosis induced by thioacetamide (TAA) was investigated. Rats were divided into seven groups: control, lesimarin, TAA, TAA+lesimarin, TAA+lecithin, TAA+silymarin, TAA+AMB. Rats were administered with TAA at a dose of 200 mg/kg body weight intraperitoneally twice a week for three months. Lesimarin, lecithin, silymarin and AMB were administered at a dose of 1.0, 1.0, 0.5, 1.0g/kg body weight orally daily for three months, respectively. TAA administration resulted in hepatic fibrosis, significant decrease in body weight, albumin level and A/G ratio and increase in plasma transaminase, GGT(γ-glutamyltransferase) and ALP(alkaline phosphatase) activities as well as hepatic hydroxyproline content, which were attenuated by lesimarin administration. Lesimarin was found to decrease AST, ALT and GGT, ALP and bilirubin, hydroxyproline levels and increase albumin level and A/G ratio and its effect is more prominent than those of individual constituents. These results suggest this new drug, lesimarin, might be a promising drug to be used for chronic liver diseases.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson's trichrome staining. Transforming growth factor-beta 1 (TGF-β1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1β levels, MDA level, TGF-β1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-β1 and iNOS signaling pathways. [ABSTRACT FROM AUTHOR]

The article deals with the choice of diuretic in arterial hypertension and presents data on the antihypertensive efficacy of the loop diuretic torasemide. Data on the mechanisms of antihypertensive action of torasemide are presented, including a unique antialdosterone effect. The article reports on the absence of a negative effect of the drug on carbohydrate, lipid, purine metabolism and electrolyte balance, positive effect on the target organs, very good tolerability. It is advisable to use torasemide more widely in a "non-diuretic" dose (2.5-5 mg / day) for the treatment of arterial hypertension as in monotherapy as in combination with other antihypertensive drugs.

The article deals with the choice of diuretic in arterial hypertension and presents data on the antihypertensive efficacy of the loop diuretic torasemide. Data on the mechanisms of antihypertensive action of torasemide are presented, including a unique antialdosterone effect. The article reports on the absence of a negative effect of the drug on carbohydrate, lipid, purine metabolism and electrolyte balance, positive effect on the target organs, very good tolerability. It is advisable to use torasemide more widely in a "non-diuretic" dose (2.5-5 mg / day) for the treatment of arterial hypertension as in monotherapy as in combination with other antihypertensive drugs.

Background: Tumor necrosis factor (TNF)-α can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-α by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-α-induced PAI-1 upregulation and the underlying mechanisms were evaluated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. Results: Adp decreased the TNF-α-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-α-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-α-induced NF-kB binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. Conclusions: Our data suggest that Adp abrogates TNF-α-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NF-kB binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases.

Abstract Background Idiopathic pulmonary fibrosis is a lethal fibrosing interstitial pneumonia characterized by progressive worsening of dyspnea and lung function with poor prognosis. Since pirfenidone was approved for IPF treatment, the search for more effective candidates has been greatly intensified. Methods In this study, the antifibrotic effects and mechanisms of compound PBD-617 , the ideal candidate discovered in our previous work, were investigated on transforming growth factor-β1 (TGF-β1)-induced human embryonic lung fibroblasts (HELF) and on bleomycin (BLM)-induced pulmonary fibrotic rats. Results Oral administration with PBD-617 decreased the levels of collagen I, collagen III and matrix metalloproteinase 7, and inhibited the protein expression of α-smooth muscle actin in BLM-induced pulmonary fibrosis rats. Furthermore, PBD-617 suppressed the expression of TGF-β1, phosphorylated Smad3, phosphorylated p38 and activator protein 1 on TGF-β1-induced HELF, while the regulation could be rescued by using p38 agonist p79350. Conclusion PBD-617 not only inhibited TGF-β1-induced HELF proliferation, but also attenuated BLM-induced pulmonary fibrosis in rats, with efficacy to some extent higher than that of pirfenidone at the same effective dosage. PBD-617 attenuated pulmonary fibrosis effectively by suppressing activation of TGF-β1/Smad3 and p38 signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor (TNF)-α can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-α by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-α-induced PAI-1 upregulation and the underlying mechanisms were evaluated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. Results: Adp decreased the TNF-α-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-α-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-α-induced NF-κB binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. Conclusions: Our data suggest that Adp abrogates TNF-α-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NF-κB binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases. [ABSTRACT FROM AUTHOR]

Objectives. Folate receptor β (FRβ)-expressing macrophages have been identified as activated macrophages. Here, we investigated the infiltration of FRβ-expressing macrophages in a murine model of bleomycin (BLM)-induced skin fibrosis and assessed the antifibrotic effects of depletion of FRβ-expressing macrophages in this model using a recombinant immunotoxin to FRβ. Methods. A recombinant immunotoxin (anti-FRβ-PE38) was prepared by conjugating the Fv portion of the anti-mouse FRβ heavy chain with truncated Pseudomonas exotoxin A (VH-PE38) and the Fv portion of the anti-mouse FRβ light chain. BLM-induced skin fibrosis mice were intravenously treated with either anti-FRβ-PE38 or VH-PE38 as a control protein. Skin fibrosis was evaluated by the change of skin thickness and hydroxyproline content on Day 29. The TGFβ1 mRNA levels in the treated skin were assessed by quantitative real-time RT-PCR on Day 9. Results. Numbers of FRβ-expressing macrophages increased in BLM-injected skin. Anti-FRβ-PE38 treatment led to a dramatic reduction in the number of FRβ-expressing macrophages. Additionally, skin thickness and hydroxyproline content, were markedly reduced. TGFβ1 mRNA levels were also down-regulated after the treatment. TGFβ1 expression was enriched in FRβ-expressing macrophages compared with FRβ-negative macrophages. Conclusion. These results indicated that anti-FRβ-PE38 treatment efficiently depleted FRβ-expressing macrophages and consequently alleviated BLM-induced skin fibrosis. [ABSTRACT FROM AUTHOR]

Objective: The effects of pirfenidone were investigated on cultured human pterygium fibroblasts (HPFs). Methods: HPFs were obtained from pterygium surgery and subjected to primary culture. After treatment with 0.5, 1.0 or 1.5 mg/mL pirfenidone, MTT and cell migration assays were performed, and procollagen secretion and TGF-β expression were measured by Western blotting and immunofluorescence analysis. Results: Pirfenidone had a significant inhibitory effect on HPF proliferation, migration and collagen synthesis. There were no differences between the cells treated with 0.5, 1.0 and 1.5 mg/mL pirfenidone and the controls in the MTT assay. After 48 h of treatment with 1.0 or 1.5 mg/mL pirfenidone, TGF-β expression was significantly decreased. Conclusions: These findings demonstrate that pirfenidone inhibits the proliferation, migration and procollagen secretion of HPFs at nontoxic concentrations by decreasing TGF-β expression. Thus, pirfenidone may be considered as a safe adjuvant for pterygium surgery to prevent recurrence. [ABSTRACT FROM AUTHOR]

Silymarin is an herbal product showing potential as protection against hepatic disorders. In an attempt to develop the agent for the treatment of hepatic fibrosis, we screened the effects of silymarin on a rat model of hepatic fibrosis induced by carbon tetrachloride (CCl4). Intraperitoneal administration of CCl4 to rats for 8 weeks not only increased the plasma levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) but also induced a marked increase in the formation of hepatic fibrosis. Moreover, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were also reduced in the liver of rats treated with CCl4. Oral administration of silymarin (200 mg/kg, three times daily), in parallel, decreased the plasma levels of GOT and GPT. Furthermore, in addition to the improvement of hepatic fibrosis, the hepatic levels of hydroxyproline and connective tissue growth factor (CTGF) were both markedly decreased by silymarin. Silymarin also elevated the activities of SOD and GPx in liver isolated from CCl4-treated rats. The results suggest that oral administration of silymarin protects against CCl4-induced hepatic fibrosis in rats, likely due to the decrease in fibrotic parameters such as CTGF. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have reported the herbal medicine Inchinko-to (ICKT) to have an antifibrotic effect which thus leads to an improvement of hepatic injury. However, there are still few reports of its use in the treatment of cholestatic liver disorder. The aim of this study was to clarify whether the administration of ICKT will ameliorate hepatic fibrosis and injury in cholestatic rats. Materials and methods: We performed bile duct ligation on 7-week-old male cholestatic Wistar rats and assigned them to one of three groups according to the method of treatment : (1) the SHAM group, (2) the NT-group (non-treatment group), and (3) the T-group (treatment-group). Rats in the T-group were orally administered ICKT (TJ-135) at a dose of 1 g/kg/day and were killed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and various clinical markers through measurement of the following: serum levels of AST and ALT; tissue transforming growth factor-beta 1 (TGF-beta1); tissue inhibitor metalloprotease-1 mRNA (TIMP-1 mRNA) through real-time PCR analysis; and Azan staining and immunohistochemical staining of alfa-smooth muscle actin (alfa-SMA) to evaluate the degree of fibrosis. Results: The levels of serum AST, serum ALT, and TGF-bata1 in the T-Group were significantly lower than those in the NT-Group. In addition, staining of Azan and alfa-SMA in the T-Group was significantly lower than those in the NT-Group. Conclusion: ICKT may help reduce hepatic fibrosis and injury by controlling stellate cell activation. [ABSTRACT FROM AUTHOR]

To compare the antifibrotic effect of vitamin E isoforms α-, γ-, and δ-tocotrienol on human Tenon’s fibroblasts (hTf) to the antimetabolite mitomycin C. Antifibrotic effects of α- (40, 60, 80, 100, and 120 μM), γ- (10, 20, 30, and 40 μM) and δ-tocotrienol (10, 20, 30, and 40 μM) on hTf cultures were evaluated by performing proliferation, migration and collagen synthesis assays. Whereas for vitamin E the exposure time was set to 7 days to mimic subconjunctival application, cultures were exposed only 5 min to mitomycin C 100 μg/ml to mimic intraoperative administration. Cell morphology (phase contrast microscopy) as an assessment for cytotoxicity and cell density by measuring DNA content in a fluorometric assay to determine proliferation inhibition was performed on day 0, 4, and 7. Migration ability and collagen synthesis of fibroblasts were measured. All tested tocotrienol isoforms were able to significantly inhibit hTf proliferation in a dose-dependent manner (maximal inhibitory effect without relevant morphological changes at day 4 for α-tocotrienol 80 μM with 36.7% and at day 7 for α-tocotrienol 80 μM with 42.6% compared to control). Degenerative cell changes were observed in cultures with concentrations above 80 μM for α- and above 30 μM for γ- and δ-tocotrienol. The highest collagen synthesis inhibition has been found with 80 µM α-tocotrienol (62.4%) and no significant inhibition for mitomycin C (2.5%). Migration ability was significantly reduced in cultures exposed to 80 µM α- and 30 µM γ-tocotrienol (inhibition of 82.2% and 79.5%, respectively, compared to control) and also after mitomycin C treatment (60.0%). Complete growth inhibition without significant degenerative cell changes could only be achieved with mitomycin C. In vitro, all tested tocotrienol isoforms were able to inhibit proliferation, migration and collagen synthesis of human Tenon’s fibroblasts and therefore may have the potential as an anti-scarring agent in filtrating glaucoma surgery. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Saururus chinensis (Lour.) Baill (Saururaceae) has been used in Chinese folk medicine for treatment of various diseases, such as edema, jaundice, gonorrhea, antipyretic, diuretic, and antiinflammatory agents. Aim of the study: Our aim was to evaluate the hepatoprotective and antifibrotic effects of Saururus chinensis extract (SC-E) in carbon tetrachloride (CCl4) induced liver fibrosis rats. Materials and methods: The SC-E (70mg/kg) was administrated via gavage once a day starting from the onset of CCl4 treatment (14 weeks) for subsequent 8 weeks. Evaluated with liver index, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), hepatic malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity, total cholesterol (TC), triglyceride (TG), total lipoprotein (TP), albumin (ALB), hydroxyproline (HYP), total antioxidant capacity (T-AOC), laminin (LN), type III collagen terminal peptide (PC-IIINP), and type IV collagen (IV-C), as well as with histopathologic changes of liver. Results: SC-E effectively reduced the elevated levels of liver index, serum ALT, AST, HA, and hepatic MDA contents, enhance the reduced hepatic SOD activity in CCl4-treated rats. The histopathological analysis suggested that SC-E obviously alleviated the degree of liver fibrosis induced by CCl4. Conclusions: Those results suggest SC-E has protective and therapeutic effects on liver fibrosis induced by CCl4. [Copyright &y& Elsevier]

The antifibrotic effect of heparin, an anticoagulant used routinely in the treatment of peritonitis, is unknown, whereas antithrombin III (AT-III) has both anticoagulant and anti-inflammatory actions. The aim of this study was to compare the antifibrotic and anti-inflammatory effects of AT-III and heparin in rats with experimentally developed peritonitis while on peritoneal dialysis (PD). Sixty-four Wistar albino rats (in four groups of 16) were used in the study. Group 1 received PD solution only, group 2 had experimentally developed peritonitis in addition to PD solution; group 3 received heparin intraperitoneally for 3 days, in addition to group 2; and group 4 received AT-III intraperitoneally for 3 days, in addition to group 2. Plasma and dialysate levels of tissue-plasminogen activator were similar in heparin and AT-III groups on both day 3 and day 14. The inflammation scores of heparin and AT-III groups were also similar in both early and late phases. The fibrosis score of the AT-III group was low compared with both peritonitis and heparin groups in the early phase ( p = 0.03), though it was similar in the late phase. The effects of AT-III are comparable with that of heparin in PD peritonitis in rats with experimentally developed peritonitis while on PD. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Data from studies in other diseases state implicate cellular adhesion molecules as mediators of fibrosis and scarring. We sought to explore and assess the effect of using monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) and its ligand CD-18 to decrease epidural fibrosis in an animal spinal surgery model. Purpose: We hypothesize that use of antiadhesion molecules (anti–ICAM-1 and anti–CD-18) decreases epidural fibrosis in rats after spinal surgery compared with nontreated group and monoclonal anti human immunoglobulin (Ig)G group. Study design: Experimental animal spine surgery (laminectomy) protocol with application of antiadhesion molecules (anti–ICAM-1 and anti–CD-18 group as a specific monoclonal antibody) to surgical site in test group compared with monoclonal antihuman IgG group (as a nonspecific monoclonal antibody) and nontreated group. Methods: Thirty Sprague Dawley male or female rats weighing 175 to 250 g were used randomly for three groups (nontreated, anti–ICAM-1 and anti–CD-18, monoclonal antihuman IgG). Laminectomy was performed at level L4 in all animal groups. After injection of materials (except nontreated group), the surgical sites were closed in layers. Three weeks later, all rats were killed. Twenty-seven rats were available for histological analysis. The histological sections were evaluated for fibroblast numbers of fibrous tissue within the laminectomy side, adhesion degree between dura mater and fibrous tissue, and new bone formation in the laminectomy region. Results: Comparing the fibroblast numbers in fibrous tissue within groups, the number of fibroblasts were significantly less in anti–ICAM-1 and anti–CD-18 group than nontreated group (p=.037). The number of fibroblasts of monoclonal anti human IgG group was not significantly different from anti–ICAM-1 and anti–CD-18 (p=.608) and the nontreated group (p=.508). In the anti–ICAM-1 and anti–CD-18 applied group, adhesion degree was found significantly less than monoclonal antihuman IgG (p=.036) and nontreated group (p=.036) statistically. There were no significant difference between the monoclonal antihuman IgG group and the nontreated group about adhesion degree (p=.645). Conclusions: Therapy that targets ICAM-1 could be valuable in the management of epidural fibrosis. Blocking the function of ICAM-1 may provide cellular protection against epidural fibrosis and also it may serve as an important component in this period, acting to promote leukocyte migration across epidural area after laminectomy. [Copyright &y& Elsevier]

Abstract: This study presents the antifibrotic effect of interferon gamma (IFN-γ) in silicosis of rats. Wistar rats were received saline or 20mg of quartz by intratracheal instillation. The next day after instillation, silicosis model of rats were daily treated IFN-γ (1.0×105units/rat) or saline by intramuscular route. At 1 month or 2 months after instillation, rats were sacrificed to determine hydroxyproline content and observe the change of fibrosis and expression of interleukin-4 (IL-4) and transforming growth factor-β1 (TGF-β1) in the lung of rats. The hydroxyproline content of IFN-γ treated groups was significantly lower than that of quartz groups (P<0.05). At 1 month after instillation, there were Stage II and II+ of silicotic nodules in quartz group; however, in IFN-γ treated group only cellular nodules (Stage I) were observed. At 2 months after instillation, there was Stage II+ and III of silicotic nodules in quartz group. In IFN-γ treated group Stage II was found. The expressions of IL-4 (2.19±0.90, 0.61±0.22, respectively) and TGF-β1 (1.37±0.31, 1.76±0.72, respectively) in IFN-γ treated groups were significantly lower than those in quartz groups (IL-4: 3.33±1.27, 1.99±0.80; TGF-β1: 3.67±0.63, 4.90±1.11, respectively; P<0.05 or P<0.01). It may be concluded that the decreased expression of IL-4 and TGF-β1 may be associated with decreased hydroxyproline synthesis, which then results in decreased lung fibrosis. [Copyright &y& Elsevier]

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Objective: To screen 14 different plant extracts for their antifibrotic effect on human primary leiomyoma and healthy myometrial cells., Design: Preclinical study., Setting: University research laboratory., Patient(s): Human uterine leiomyoma and matched myometrial tissues were obtained from Caucasian premenopausal women with symptomatic uterine fibroids at the time of hysterectomy., Intervention(s): Primary human leiomyoma and myometrial cells were cultured in the absence or presence of the plant extracts., Main Outcome Measure(s): Quantification of the expression of extracellular matrix components, such as fibronectin 1 (FN1), collagen type I alpha 1 (COL1A1), and versican (VCAN), and the profibrotic growth factor activin A or inhibin beta A subunit (INHBA)., Result(s): The cells were treated with the 14 extracts for 48 hours, and we measured FN1 messenger RNA (mRNA) expression. Of the 14 extracts, about (ABO) ABO-2 (hop) and ABO-9 (artichoke) significantly reduced FN1 expression in both the cell types. Next, we evaluated the effect of fractions of these 2 extracts on the mRNA expression of FN1 and other extracellular matrix components, such as COL1A1, VCAN, and INHBA, in leiomyoma and myometrial cells. We found that ABO-2 (hop) and ABO-9 (artichoke) as well as their fractions, ABO-AR-2016-015 (fraction of ABO-2) and ABO-AR-2014-168 (fraction of ABO-9), reduced the mRNA expression of FN1, COL1A1, VCAN, and INHBA in primary leiomyoma cells. In primary myometrial cells, the mRNA expression of FN1, COL1A1, VCAN, and INHBA was not greatly affected., Conclusion(s): These results suggest that the hop and artichoke extracts possess antifibrotic properties and support additional evaluation using in vivo models., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Mineralocorticoid receptor antagonists have been successfully used for many years to treat patients with primary hyperaldosteronism, refractory arterial hypertension and chronic heart failure. The increased interest in this drug in recent years is due to new information about its antifibrotic and antiproliferative effects, both cardiac and extracardiac. The article also discusses the possibility of using spironolactone in patients with the new coronavirus infection SARS-CoV-2 (COVID-19).

End-stage renal disease is a worldwide epidemic requiring renal replacement therapy. Harvesting tissue from failing kidneys and autotransplantation of tissue progenitors could theoretically delay the need for dialysis. Here we use healthy and end-stage human adult kidneys to robustly expand proliferative kidney epithelial cells and establish 3D kidney epithelial cultures termed "nephrospheres." Formation of nephrospheres reestablishes renal identity and function in primary cultures. Transplantation into NOD/SCID mice shows that nephrospheres restore self-organogenetic properties lost in monolayer cultures, allowing long-term engraftment as tubular structures, potentially adding nephron segments and demonstrating self-organization as critical to survival. Furthermore, long-term tubular engraftment of nephrospheres is functionally beneficial in murine models of chronic kidney disease. Remarkably, nephrospheres inhibit pro-fibrotic collagen production in cultured fibroblasts via paracrine modulation, while transplanted nephrospheres induce transcriptional signatures of proliferation and release from quiescence, suggesting re-activation of endogenous repair. These data support the use of human nephrospheres for renal cell therapy. • Growing human renal epithelial cells in 3D restores epithelial identity lost in 2D • These 3D nephrospheres (nSPHs) organize into renal tubular structures in vivo • By doing so, nSPHs engraft long term and improve renal function in CKD mice • In vivo repair involves anti-fibrotic effects and possible addition of nephron segments Human kidney cells quickly degenerate in culture, precluding them as a source for cell therapy for chronic kidney disease (CKD). Herein, Harari-Steinberg et al. show that upon culturing as 3D nephrospheres, human kidney cells regain their epithelial phenotype and acquire in vivo tissue-forming and reparative properties in a CKD mouse model. [ABSTRACT FROM AUTHOR]

Abstract: This study was carried out to evaluate the antifibrotic effect of ethanol extract of the fruits of Indian herb Piper longum Linn. Liver fibrosis was induced in rats by CCl4 administration. The extent of liver fibrosis was assessed by measuring the level of liver hydroxy proline (HP) and serum enzyme levels. Following CCl4 administration HP was significantly increased and serum enzyme levels were elevated. Treatment with the ethanol extract of Piper longum Linn. reduced the HP and also the serum enzymes. The liver weight that increased following CCl4 administration due to the deposition of collagen was reduced by the ethanol extract. Hence, it is concluded that this extract inhibits liver fibrosis induced by CCl4. [Copyright &y& Elsevier]

Fuzheng Huayu formula (FZHY) is a traditional Chinese medicine formula composed of Radix Salvia Miltiorrhizae , Cordyceps , Semen Persicae , Gynostemma Pentaphyllammak, Pollen Pini , Fructus Schisandrae Chinensis that is used to treat chronic liver diseases in China. We here describe the pharmacological actions of FZHY in this review. We also describe and provide updates on recent advances in the medical applications and the basic research of mechanisms of FZHY formula. FZHY has been shown to have no serious adverse reactions and exerts antifibrotic effects through targeting more than one molecule. [ABSTRACT FROM AUTHOR]