Chemical components in cultivated Cordyceps sinensis and their effects on fibrosis / 中草药·英文版

OBJECTIVE@#Cultivated Cordyceps sinensis powder has been used as clinical drug and healthy food to nourish the lung and kidney, which solves the problem of serious shortage of wild C. sinensis. This study aims to explore the chemical components and compared their anti-fibrotic effects in cultivated C. sinensis.@*METHODS@#Nucleosides, sterols and polysaccharides were separated and purified from cultivated C. sinensis, and analyzed by high performance liquid chromatography, gas chromatography-mass spectrometry and chemical chromogenic methods, respectively. In high glucose-induced rat mesangial cell models, fibronectin and type 1 collagen were used as evaluation indicators.@*RESULTS@#There were 10 kinds of nucleosides and one sterol in cultivated C. sinensis. The contents of nucleosides, sterols and polysaccharides in the cultivated C. sinensis were close to 2%, 0.55% and 4.4%, respectively. Furthermore, nucleoside, sterol and polysaccharide components exhibited varying degrees of anti-fibrotic activity. The nucleoside components and sterol components inhibited the expression of extracellular matrix more effectively in the three main components.@*CONCLUSION@#Cultivated C. sinensis remains the similar compounds with the wild C. sinensis, and nucleosides and sterols may be the main active substances that contribute to its anti-fibrotic effects. The project of this study may provide valuable information on further optimization of more effective remedies with few side effects based on cultivated C. sinensis.

The action of subconjunctival cyclophosphamide in rabbits / Ação da ciclofosfamida subconjuntival em coelhos

ABSTRACT Objective: To observe clinically, in rabbits, the side effects of topical injection of subconjunctival cyclophosphamide, studying its role as an antifibrotic drug. Methods: Prospective study in 20 albino rabbits of New Zealand race. All rabbits were treated with cyclophosphamide, 10mg/ml in a volume of 0.3 ml, in the left eye through subconjunctival injection. They were evaluated for 1, 7, 30, and 60 days after the procedure. All the animals were examined for the detection of ocular reactions such as necrosis, hyperemia, chemosis, secretion, opacity, and iritis. Other side effects as changes in the behavior, in the feed, and the water consumption were also evaluated. Results: It was observed that from the 20 rabbits studied, three rabbits (15%) showed side effects only at the 24 hours analysis. One rabbit (5%) presented hyperemia, one rabbit (5%) had hyperemia associated with iritis, and one rabbit (5%) presented hyperemia associated with secretion. These reactions were not observed at 1, 7, 30, and 60 days. Conclusion: Cyclophosphamide subconjunctival injection induces minor side effects on the conjunctiva of rabbits such as hyperemia, associated with iritis and secretion.

RESUMO Objetivo: Observar clinicamente os efeitos colaterais de injeção subconjuntival de ciclofosfamida, pensando em sua ação como um agente antifibrótico. Métodos: Estudo prospectivo realizado com 20 coelhos albinos da raça Nova Zelândia. Todos os coelhos foram submetidos a 0,3 ml de injeção subconjuntival de ciclofosfamida 10mg/ml no olho esquerdo e foram avaliados de acordo com os efeitos locais no primeiro dia após a injeção, 7, 30 e 60 dias. Foram examinados para detecção de reações oculares como necrose, hiperemia, quemose, secreção, opacidade corneana, irite além de alterações comportamentais e variação no consumo de água e alimentação. Resultados: Dos 20 coelhos estudados, apenas 3 apresentaram reações oculares e somente na leitura de 24 horas. Um coelho (5%) apresentou hiperemia, 1 coelho (5%) apresentou hiperemia associada a presença de irite e 1 coelho (5%) apresentou hiperemia associada a presença de secreção. As reações não foram mais observadas durante os exames de 7, 30 e 60 dias. Conclusão: A ciclofosfamida subconjuntival causou poucos efeitos colaterais na conjuntiva dos coelhos. Os únicos efeitos encontrados foram hiperemia, irite e secreção.

Advances in the research of anti-organ fibrosis drugs / 药学学报

Fibrosis is a pathological process characterized by tissue scars and can occur in many organs of the human body. Organ fibrosis is manifested by increased fibrous connective tissue and reduced parenchymal cells in organ tissues, which can lead to destruction of organ structures and reduced function, which seriously endangers human health. Current strategies for treating organ fibrosis include: blocking the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, anti-inflammatory, regulating the sphingosine kinase 1/sphingosine-1-phosphate (SK1/S1P) signaling pathway, antagonizing vasoactive peptide receptors, enzyme inhibitors, kinase inhibitors, inhibitors of cellular signaling pathway, regulation of metabolic pathways, and mesenchymal stem cell therapy. In the review, the treatment strategies for organ fibrosis and the latest developments in the research of anti-organ fibrosis drugs are summarized to provide a reference for the development of anti-organ fibrosis drugs.

Therapeutic mechanism of adipose mesenchymal stem cells in mice with systemic sclerosis / 中国组织工程研究

BACKGROUND: Although clinical studies have found that autologous adipose mesenchymal stem cells can effectively reduce facial fibrosis in patients with radiation-induced systemic sclerosis, but the mechanism of action has not been thoroughly analyzed. OBJECTIVE: To study the mechanism of action of adipose mesenchymal stem cells on bleomycin-induced systemic sclerosis in mice. METHODS: Forty SPF C57BL/6J female mice aged 6-8 weeks were randomly assigned to normal control group, adipose mesenchymal stem cells group, bleomycin group, and PBS group. Mice in the latter three groups were subjected to subcutaneous injection with bleomycin every other day for 28 days, and mouse models of systemic sclerosis were established. After successful model establishment, mice in the adipose mesenchymal stem cells group were subcutaneously injected with adipose mesenchymal stem cells; mice in the PBS group were subcutaneously injected with PBS; the treatments lasted for 14 days. Enzyme-linked immunosorbent assay was used to determine the levels of serum interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α. Hematoxylin-eosin staining and Masson staining were utilized to measure histopathological changes in the skin and lung of systemic sclerosis mice. Immunofluorescence method was applied to examine collagen I, III, and V and CD31 expression levels in the skin and lung. RESULTS AND CONCLUSION: (1) Compared with the bleomycin group, the expression levels of interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α were significantly decreased in the adipose mesenchymal stem cells group (P < 0.01). (2) Compared with the normal control group, the skin dermis of mice was thickened; inflammatory cells infiltrated; skin appendages reduced; the alveoli were atrophic and collapsed; with a lot of inflammatory cell infiltration, pulmonary arteriole wall thickening, microvascular basement membrane thickening, and fibrinoid necrosis, and the inflammatory symptoms improved after treatment in the adipose mesenchymal stem cells group. (3) Compared with the normal control group, the skin and lung tissues of bleomycin group mice showed a large aggregation of collagen fibers, and the collagen fibers were reduced after adipose mesenchymal stem cells treatment. (4) After treatment with adipose mesenchymal stem cells, the expression levels of collagen I, III, and V were decreased in the skin and lung tissue of mice, but the expression of CD31 in the skin tissues was increased in the bleomycin group (P < 0.01). (5) The results suggested that adipose mesenchymal stem cells can regulate the immune response of bleomycin mice and reduce fibrosis, inflammation and vascular lesions.

Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix, and no specific medical therapy is approved for that until now. Due to liver metabolic capacity for drugs, the fragility of drugs, and the presence of insurmountable physiological obstacles in the way of targeting, the development of efficient drug delivery systems for anti-fibrotics seems vital. We have explored articles with a different perspective on liver fibrosis over the two decades, then collected and summarized the information by providing corresponding  and  cases. We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals. Furthermore, the critical chemical and herbal anti-fibrotics, biological molecules such as micro-RNAs, siRNAs, and growth factors, which can affect cell division and differentiation, are mentioned. Likewise, drug and gene delivery and therapeutic systems on  and  models are summarized in the data tables. This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the issues of bioavailability, drug design, and nano-formulation, in order to achieve successful clinical outcomes with promising activity and tolerability.

In vivo Antifibrotic Potential of Extracts of Acanthospermum hispidum DC. Evaluated in Wistar Rats Using Diethylnitrosamine

Aims: Liver fibrosis is a chronic disease of the liver. This disease is a stage of passage to liver cancer. The objective of this work was to evaluate the ability of the ethanolic extract of Acanthospermum hispidumto block the progression of hepatic fibrosis induced in rats using diethylenitrosamine (DEN).Study Design:Study of the antifibrotic potential of extracts of Acanthospermum hispidum.Place and Duration of Study:In vivotests were performed from September 2018 to January 2019. The animal model tests were carried out in the pet shop of the Institute for Health Sciences Research (IRSS) of Burkina Faso and in the Cytogenetics Laboratory (FSS/ISBA) of the Republic of Benin.Methodology:The evaluationof the antifibrotic activity consisted in treating in wistarrats a liver fibrosis induced with the DEN which is a chemical agent whose effect on the liver has already been confirmed. As a result of the treatment, all animals were removed from the liver and blood. The livers were used for macroscopic and microscopic observations. Blood has been used for the evaluation of biochemical parameters in relation to fibrosis.Results:The analysis of the results of the biochemical parameters in relation to the fibrosis showed that the ethanolic extract of Acanthospermum hispidumat the dose of 250 mg / kg made it possible to obtain an improvement of these parameters compared to the other batches of animals. These results have been confirmed by those of the anatomo-pathological studies.Conclusion:The results of biochemical and histological analyzes revealed a capacity of Acanthospermum hispidumextracts to block the evolution of hepatic fibrosis in the rat. These results confirm the hepatoprotective potential of this medicinal plant used in traditional medicine in Burkina Faso

A brief review on Pleiotropic effects of Pirfenidone - novel and ongoing outcomes

Presently, there is a huge hype and excitement in the field of synthetic biologics and engineering regarding growing cases of their implication in various fields including health care systems. Furthermore, despite its large body of suggestive and fascinating accomplishments, the synthetic area is always been subject of much more prejudice and debate. However, over a couple of years, the generation of researchers had tested one of such disease modifying compound Pirfenidone (Esbriet®), to unleash their potential in the different disciplines of interventional pharmacology and therapy. In this pipeline, depending on its success of multiple missions, in context to advancing the therapy for different diseases, it became the first prescribed medicine to treat the people with one characteristic lung disorder called idiopathic pulmonary fibrosis (IPF). This review discusses the different therapeutic strategies beyond its well-known anti-fibrotic activity in several well-characterized animals, cell-based and human models and also regarding facts of Pirfenidone (PFD) as anti-inflammatory, anti-fibrinogenic, anti-oxidants including in the treatment of diabetic neuropathy, liver cirrhosis etc. This review also contains current investigations, focusing mainly on the novel findings and their outcomes in improving the quality of life of patients with different conditions and also suggests their implication on the basis of fundamental existential evidences to break the major impediment in transforming this disease-modifying drug into a personalized medicine.

Ethanol Extract of Centella asiatica (Gotu Kola) Attenuates Tubular Injury Through Inhibition of Inflammatory Cytokines and Enhancement of Anti-Fibrotic Factor in Mice with 5/6 Subtotal Nephrectomy

@#Background: Chronic kidney disease (CKD) leads to inflammation, fibrosis and destruction of the renal architecture. Centella asiatica (CeA) is an herbaceous plant with antiinflammatory effects. We aimed to elucidate the effect of CeA on inflammation, fibrosis, vascular remodelling and antifibrotic substances in a 5/6 subtotal nephrectomy (SN) model in mice. Methods: Mice were divided into three groups: sham operation (SO, n = 6), 5/6 SN for seven days (SN7, n = 7) and SN7 with oral CeA treatment (SN7-CeA, n = 7). At day 7, mice were euthanised, kidneys were harvested and stained with periodic-acid Schiff (for tubular injury and glomerulosclerosis) and sirius red (for fibrosis and vascular remodeling) staining. mRNA expression of prepro-endothelin-1, nephrin, E-cadherin, bone morphogenic protein-7 (BMP-7), toll-like receptor 4 (TLR4), tumour necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) were quantified using reverse transcriptase-PCR. Results: SN group demonstrated significant higher interstitial fibrosis, vascular remodeling, tubular injury and glomerulosclerosis (P < 0.01) compared to SO group. Meanwhile, in SN7-CeA demonstrated attenuation of vascular remodeling as shown by significant higher lumen area with lower Wall/Lumen area ratio compared to SN7. RT-PCR analysis showed up-regulation of nephrin, BMP-7 and E-cadherin mRNA expression (P < 0.05) and down-regulation of ppET-1 in SN7-CeA group compared to SN7 group (P < 0.05). Conclusion: CeA may ameliorate renal injury in the SN model in mice.

Research Progress of Two New Antifibrotic Drugs for Idiopathic Pulmonary Fibrosis / 中国药学杂志

Pirfenidone and nintadanib are two new anti-fibrotic drugs that have been shown to reduce the decline of lung function in patients with idiopathic pulmonary fibrosis (IPF) in multiple clinical trials,and have become first-line drugs for the treatment of IPF.However there are lack of references for how to choose between these two drugs. This article collected the latest research literatures related to pirfenidone or nintedanib,and summarized pharmacokinetics, pharmacological mechanism, clinical trials and safety profile of pirfenidone and nintedanib, so as to provide reference for clinical drug use. Evidences show both pirfenidone and nintedanib can reduce the decline of lung function and delay disease progression in mild-to-moderte IPF patients, and may have similar effects on severe IPF patients. There are large differences in pharmacological mechanisms, pharmacokinetics, and adverse events between these two new antifibrotic drugs. However, in terms of efficacy, there is no clear evidence to show which drug is better. Clinicians choosing drug should base on pharmacokinetic characteristics and adverse events between these two drugs.

Research progress on proteins and peptides from earthworm / 中草药

Earthworm is one of animal drugs in Chinese materia medica. It was commonly used in clinic with rich resources in China. Modern studies showed that proteins and peptides were the main components in earthworm. It has been used for treating cardiovascular and cerebrovascular diseases because of its various activities, such as anticoagulant, anti-stroke, antibacterial, and antifibrotic activities, etc. In this review, 48 proteins and peptides from different species of earthworm reported since 1983 were summarized, including their names, molecular weights, amino acid sequences, isoelectric points, and activities. In addition, its pharmacological effects of earthworm proteins and peptides were summarized. In all, it will provide a scientific basis for the further study and comprehensive utilization of proteins and peptides of earthworm.

Effect of lesimarin against thioacetamide-induced liver cirrhosis in rat

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.

Protective Effect Of Diosgenin Against Carbon Tetrachloride And Cisplatin Induced Hepatotoxicity In Rats

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor-β. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl4) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bili-rubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl4and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation.

Effect of Bevacizumab on Human Tenon's Fibroblasts Cultured from Primary and Recurrent Pterygium

The purpose of this study was to compare the inhibitory effect of bevacizumab on human Tenon's fibroblasts (HTFs) cultured from primary and recurrent pterygium. Cultured HTFs were exposed to 2.0, 5.0, 7.5, and 15.0 mg/mL concentration of bevacizumab for 24 hours. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase leakage assays were then performed to assess fibroblast metabolism and viability. The matrix metalloproteinase (MMP), procollagen type I C terminal propeptide (PIP), and laminin immunoassays were performed to examine extracellular matrix production. Changes in cellular morphology were examined by phase-contrast and transmission electron microscopy. Both metabolic activity and viability of primary and recurrent pterygium HTFs were inhibited by bevacizumab in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. Both types of HTFs had significant decreases in MMP-1, PIP, and laminin levels. Distinctly, the inhibitory effect of bevacizumab on MMP-1 level related with collagenase in primary pterygium HTFs was significantly higher than that of recurrent pterygium. Significant changes in cellular density and morphology both occurred at bevacizumab concentrations greater than 7.5 mg/mL. Only primary pterygium HTFs had a reduction in cellular density at a bevacizumab concentration of 5.0 mg/mL. Bevacizumab inhibits primary and recurrent pterygium HTFs in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. As the primary HTFs produces larger amounts of MMP-1 compared to recurrent HTFs, significant reduction in MMP-1 level in primary pterygium HTFs after exposure to bevacizumab is likely to be related to the faster cellular density changes in primary pterygium HTFs.

Augmentation of Filtering Blebs with Viscoelastics in Trabeculectomy

PURPOSE: To evaluate the clinical outcome of viscoelastics (VE, sodium hyaluronate)-augmented trabeculectomy (VAT, 66 eyes) and conventional trabeculectomy (CT, 57 eyes) for glaucomatous eyes. METHODS: In the VAT group, half of the anterior chamber space was filled with VE via the paracentesis site at the end of CT and a balanced salt solution was injected into the anterior chamber. This procedure induced migration of VE from the anterior chamber into the bleb space; thus the bleb was elevated with underlying VE. Follow-up examinations were performed until 1 year after surgery. Success was defined as the attainment of an intraocular pressure (IOP) greater than 5 mmHg and less than 22 mmHg. If IOP was in the range of success without antiglaucoma medication, it was regarded as a complete success. RESULTS: The mean postoperative IOP was significantly lower in the VAT group at postoperative 1 day, 1 week, and 1 month. The complete success rate was significantly higher in the VAT group (89%) than in the CT group (75%), though the qualified success rate was not different between the two groups. The number of IOP-lowering medications at postoperative 1 year was significantly higher in the CT group (1.30 ± 1.08 vs. 0.73 ± 0.98, p = 0.003). Among postoperative procedures, laser suture lysis was required less frequently in the VAT group (p < 0.001). CONCLUSIONS: Placing VE within the bleb at the end of surgery may result in better IOP control and less need for IOP-lowering medication without any additional materials, cost, or time.

Cytotoxicities and Anti-Fibrotic Effects of Pirfenidone and Mitomycin C on Human Fibroblasts

PURPOSE: The cytotoxicities and anti-fibrotic effects of mitomycin C and pirfenidone on human dermal fibroblast were evaluated. METHODS: Initially, 24-hour cell cultures were exposed to transforming growth factor (TGF)-beta1, different concentrations of mitomycin C, and pirfenidone solutions in order to evaluate cytotoxicity. Expressions of fibronectin, collagen type 1, alpha smooth muscle, and beta-actin were evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot in mitomycin C solutions at concentrations of 4 microg/mL and 20 microg/mL, and in pirfenidone solutions at 250 microg/mL and 500 microg/mL. RESULTS: In comparison to cell cultures exposed to TGF-beta1 solutions, cytotoxicities were increased in solutions of mitomycin C at 4 microg/mL, 20 microg/mL, 40 microg/mL and pirfenidone at 500 microg/mL, 750 microg/mL, 1,000 microg/mL (p < 0.05, Mann Whitney U-test). The results of real-time RT-PCR show that expressions of fibronectin, collagen type 1, and alpha smooth muscle were significantly more decreased in all concentrations of mitomycin C and pirfenidone compared to those in TGF-beta1 solution. In western blot analysis, expressions of fibronectin and alpha smooth muscle were decreased in all concentrations of mitomycin C and pirfenidone compared to TGF-beta1 solution. CONCLUSIONS: Both drugs have cytotoxicities and anti-fibrotic effects, but pirfenidone was found to have less cytotoxicity and mitomycin C was found to have more anti-fibrotic effects when compared to each other.

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

PURPOSE: This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 microM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated. RESULTS: Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. CONCLUSION: GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.

The Crucial Role of Cholangiocytes in Cholangiopathies

Cholangiopathies are diseases involving the intrahepatic biliary tree. They appear to involve, chronic inflammation of the bile ducts, which can lead to the development of bile duct cholestasis, proliferation/ductopenia, biliary fibrosis, and malignant transformation. Sustained stimulatory insults to biliary epithelial cells can induce a ductular reaction, which has a key role in the initiation and progression of cholangiopathies. The epithelial-mesenchymal interaction between reactive cholangiocytes and mesenchymal cells with the inflammatory infiltrates plays a major role in this pathogenesis. Cytokines, chemokines, growth factors and morphogens mediate these interactions in an autocrine or paracrine manner. The main hepatic myofibroblasts (MFs) in cholangiopathies originate from portal fibroblasts. Hepatic stellate cells and fibrocytes also transform into MFs. Whether cholangiocytes or hepatocytes are a source of MFs via the epithelial-mesenchymal transition (EMT) remains a matter of controversy. Although there have been numerous indirect findings supporting the theory of a cholangiocyte EMT in human tissues, recent studies using lineage tracing methods have demonstrated strong evidence against the EMT. Understanding the pathogenic mechanisms involved in cholangiopathies can allow for better-targeted anti-fibrotic therapies in animal models. Before anti-fibrotic therapies can translate into clinical trials, improved monitoring of the fibrotic progression of cholangiopathies and an accurate assessment regarding the effectiveness of the proposed treatments must be achieved.

Glaucoma Filtering Surgery With Low Concentration of Cyclosporin A in Rabbits: A Pilot Study

PURPOSE: The effect of 0.2% cyclosporin A (CsA) as an adjuvant therapy after glaucoma-filtering surgery was the focus of this study. METHODS: A posterior lip sclerotomy was performed in 16 eyes of 8 rabbits, and 0.2% CsA was administered into the right eyes. The left eyes served as controls. The intraocular pressure (IOP) was measured 1, 3, 5, 7, 14, and 28 days after surgery. Hematoxylin-eosin (HE) and anti-bromodeoxyuridine (BrdU) immunocytochemical staining were performed at 1, 2, 4, and 8 weeks. RESULTS: The IOP at 7 and 14 days after surgery was lower in the 0.2% CsA group and statistically significant (P=0.047, P=0.48; respectively). HE staining did not show any difference between experimental and control eyes, but anti-BrdU staining showed a lower number of positive cells in the experimental eyes at 1 week. The fibroblast proliferation rate was significantly lower 1 week after surgery in the 0.2% CsA group (P=0.003). CONCLUSIONS: An effect of 0.2% CsA on early wound healing was observed. The data suggest that a low concentration of CsA can be useful when employed as adjuvant therapy in glaucoma filtering surgery.

Efecto antifibrótico del interefrón alfa 2b recombinante en la cirrosis hepática por virus B o C / Antifibrotic effect of recombinant interferon alfa 2b in liver cirrhosis caused by virus B or C

Se evaluó el efecto antifibrótico del interferón alfa 2b recombinante utilizado durante un año (6 millones de U 3 veces a la semana) en pacientes con cirrosis hepática por virus B o C mediante estudios histológicos y de ecografía Doppler antes de concluido el tratamiento y después. Se valoró el perfil bioquímico hepático durante ese año. Participaron en la investigación 10 pacientes. Se encontró en el análisis global del método morfométrico aplicado al estudio histológico y en la ecografía Doppler que no hubo disminución estadísticamente significativa de la fibrosis hepática, pero individualmente disminuyó en 3 de los enfermos tratados y se detuvo en uno. El método de evaluación semicuantitativo de la fibrosis en la biopsia hepática no mostró que se revirtiera el proceso fibrótico. Se detectó una mejoría estadísticamente significativa en las aminotranferasas. Se detectaron efectos adversos que coinciden con lo reportado en la literatura nacional e internacional revisada.

The antifibrotic effect of recombinant interferon alfa 2b used for a year (6 millions of U 3 times a week) in patients with liver cirrhosis caused by virus B or C was evaluated by histological studies and Doppler echography before and after concluding the treatment. The hepatic biochemical profile was assessed during that year. 10 patients participated in the research. In the global analysis of the morphometric method applied to the histological study and in the Doppler echography, it was found that there was no statistically significant reduction of liver fibrosis, but it individually decreased in 3of the patients treated and it stopped in one. The semiquantitative method for evaluating fibrosis in the liver biopsy did not show a reversion of the fibrotic process. A statistically marked improvement was observed in the aminotransferases. Adverse effects coinciding with what is reported in the national and international literature reviewed were detected.