Objective: To study the antifibrotic effects of genistein(GE) and quercetin(QU) on rat hepatic stellate HSC-T6 cell proliferation stimulated with platelet-derived growth factor (PDGF), collagen synthesis and type I pr...Objective: To study the antifibrotic effects of genistein(GE) and quercetin(QU) on rat hepatic stellate HSC-T6 cell proliferation stimulated with platelet-derived growth factor (PDGF), collagen synthesis and type I procollagen messenger RNA (mRNA) expression stimulated with transforming growth factor b1 (TGFb1). Methods: Cell proliferation was measured by crystal violet staining assay. Collagen synthesis was determined by 3H-proline incorporation assay. Type I procollagen mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). Results: GE (25~70 mmolL-1) and QU (6.25~50 mmolL-1) concentration-dependently attenuated PDGF-driven HSC-T6 cell proliferative activity. TGFb1-stimulated collagen synthesis was also reduced. This was associated with a decrease in type I procollagen mRNA expression, indicating an effect at a pretranslational level. Conclusion: GE and QU may have therapeutic potential against liver fibrosis by regulating PDGF and TGFb1 actions.展开更多
A variety of surgical techniques have traditionally been used to manage cicatricial ectropion. These techniques primarily aim at vertical lengthening of the anterior lamella and include a variety of skin flaps and gra...A variety of surgical techniques have traditionally been used to manage cicatricial ectropion. These techniques primarily aim at vertical lengthening of the anterior lamella and include a variety of skin flaps and grafts. Alternative techniques such as dermal filler injection to support the eyelid margin may also be used in the management of select patients with cicatricial ectropion. The application of different types of laser for scar revision throughout the body has rapidly evolved; similar mechanisms, principles and treatment rationale can be applied to the use of lasers in the management of cicatricial ectropion. Additionally, ablative lasers, such as Carbon Dioxide and Erbium:yttrium-aluminumgarnet lasers, may be used in the transdermal delivery of antifibrotic agents, such as interferon gamma, interferon alpha, vitamin D, triamcinolone and 5-fluorouracil, resulting in efficient target tissue penetration, limitation of systemic drug toxicity and decreased degradation. Although the combination of ablative fractional resurfacing and topical antifibrotic agents is a new treatment modality, there is a great potential for its efficient utilityin the management of periocular scarring and cicatricial ectropion. The introduction of these innovative therapeutic modalities offers ophthalmologists a greater range of possible effective treatments to address periocular scar tissue and the resultant cicatricial ectropion.展开更多
Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network pharmacology.Methods:IPF was induced in C57BL/6 mice by a ...Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network pharmacology.Methods:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day.In IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were measured.Histological alterations in lung tissues were also assessed.Moreover,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF.Results:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of mice.Moreover,trigonelline alleviated bleomycin-induced histological alterations in lung tissues.Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and TLR4.Conclusions:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF.It may be considered an antifibrotic agent for further clinical development.展开更多
In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcoho...In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcohol-associated liver disease(ALD)on human health.Given its insidious onset and increasing incidence,increasing awareness of ALD can contribute to reducing the prevalence of liver diseases.ALD comprises a spectrum of several different disorders,including liver steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.The pathogenesis of ALD is exceedingly complex.Previous studies have shown that peroxisome proliferator-activated receptors(PPARs)regulate lipid metabolism,glucose homeostasis and inflammatory responses within the organism.Additionally,their dysfunction is a major contributor to the progression of ALD.Elafibranor is an oral,dual PPARαandδagonist.The effectiveness of elafibranor in the treatment of ALD remains unclear.In this letter,we emphasize the harm of ALD and the burden it places on society.Furthermore,we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets.Additionally,we discuss the mechanisms of action of PPARαandδagonists,the significance of their antifibrotic effects on ALD and future research directions.展开更多
In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its i...In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its impact on lung function of IPF patients.PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages.It inhibits various pathways and has antifibrotic,anti-inflammatory,and antioxidant properties.Despite dosage lowering,PFD slowed IPF progression and maintained functional capacity.The 6-min walk distance test indicated that patients tolerated adverse events well,and PFD significantly reduced the incidence of progression episodes and death.Even when a single disease-progression event occurred,continuing PFD treatment had benefits.展开更多
The global incidence of nonalcoholic fatty liver disease(NAFLD)is escalating considerably.NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis,wh...The global incidence of nonalcoholic fatty liver disease(NAFLD)is escalating considerably.NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis,which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix,leading to fibrosis.Hepatocyte ballooning is a key catalyst for fibrosis progression,potentially advancing to cirrhosis and its decompensated state.Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD;therefore,those with substantial fibrosis require timely intervention.Although liver biopsy is the most reliable method for fibrosis detection,it is associated with certain risks and limitations,particularly in routine screening.Consequently,various noninvasive diagnostic techniques have been introduced.This review examines the increasing prevalence of NAFLD,evaluates the noninvasive diagnostic techniques for fibrosis,and assesses their efficacy in staging the disease.In addition,it critically appraises current and emerging antifibrotic therapies,focusing on their mechanisms,efficacy,and potential in reversing fibrosis.This review underscores the urgent need for effective therapeutic strategies,given the dire consequences of advanced fibrosis.展开更多
The incidence rate and mortality of liver fibrosis caused by various etiologies are high throughout the world. Liver fibrosis, the subsequent cirrhosis and other serious related complications threaten the health of pa...The incidence rate and mortality of liver fibrosis caused by various etiologies are high throughout the world. Liver fibrosis, the subsequent cirrhosis and other serious related complications threaten the health of patients and represent a serious medical burden;yet, there is still a lack of approved methods to prevent or reverse liver fibrosis. Therefore, effective hepatic antifibrotic drugs are urgently needed. The activation and proliferation of hepatic stellate cells are still the mechanisms of fibrosis that remain the focus of therapeutic research. In recent years, significant progress has been made in the development and applicability of antifibrosis drugs. In this review, we summarize the effectiveness and safety of available antifibrosis drugs utilizing different targets. In addition, some characteristics of antifibrosis drugs in phase II and III trials are introduced in detail.展开更多
Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both wi...Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing incidence.Therefore,there is a great impetus for development of agents targeting these conditions.Accumulating data on possible treatment options for liver fibrosis are emerging in the literature.However,despite extensive research and much effort in the field,approved agents for liver fibrosis are still lacking.In this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.展开更多
Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogene...Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease(the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.展开更多
Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and,in the more advanced stages,for the limited available curative treatment options.In fact,when lesions of diff...Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and,in the more advanced stages,for the limited available curative treatment options.In fact,when lesions of different etiologies chronically affect the liver,triggering the fibrogenesis mechanisms,damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications,expensive treatments and death in end-stage liver disease.Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis,the drugs used in liver fibrosis treatment still have a limited therapeutic effect.Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected.Hepatic stellate cells play a critical role in liver fibrogenesis,thus they are the target cells of antifibrotic therapy.The application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents(including drugs and nucleic acid)in the treatment of various pathologies,including liver disease.In this review,we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.展开更多
Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix(ECM) accumulation and degradation. The relentlessproduction and progressive accumulation of ECM can lead...Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix(ECM) accumulation and degradation. The relentlessproduction and progressive accumulation of ECM can lead to end-stage liver disease. Although significant progress has been achieved in elucidating the mechanisms of fibrogenesis, effective anti-fibrotic strategies are still lacking. Autophagy is an intracellular process of self-digestion of defective organelles to provide material recycling or energy for cell survival. Autophagy has been implicated in the pathophysiology of many human disorders including hepatic fibrosis. However, the exact relationships between autophagy and hepatic fibrosis are not totally clear and need further investigations. A new therapeutic target for liver fibrosis could be developed with a better understanding of autophagy.展开更多
Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass...Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction analysis.Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers.Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides.In addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.展开更多
OBJECTIVE: The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we a...OBJECTIVE: The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we applied randomly controlled trial to check the curative effect of Chinese herbs on patients with immunoglobulin A nephropathy (IgAN). METHODS: Twenty-six patients were randomly divided into group A (control group) treated with Western Medicine and group B (treatment group) treated with combination of Traditional Chinese Medicine (TCM) and Western Medicine. Blood and urine tests were done before treatment and after 8-week treatment. RESULTS: The levels of the main composition of ex- tracellular matrix (MC-ECM), the metabolic enzyme of ECM (ME-ECM) and some cytokines in group B decreased more obviously than those in group A after 8-week treatment. So did the level of 24-hour urine protein. However, Metal matrix protease (MMP)-2 and vascular endothelial growth factor in group B increased more obviously than those in group A after 8-week treatment. No effects on the renal function were found in both groups. CONCLUSION: Our study provided important information on using the combination of TCM with Western Medicine to inhibit the progression of renal fibrosis in patients with IgAN.展开更多
We repurposed the antifibrotic drug pirfenidone—which is approved for treatment of idiopathic lung fibrosis—in a series of patients with nonalcoholic steatohepatitis-related cirrhosis.Our report demonstrates the obs...We repurposed the antifibrotic drug pirfenidone—which is approved for treatment of idiopathic lung fibrosis—in a series of patients with nonalcoholic steatohepatitis-related cirrhosis.Our report demonstrates the observed improvements in necroinflammation and regression of cirrhosis with pirfeni-done use for 12-weeks,associated with classical hepatic repair complex features on follow-up liver biopsies.This novel work could help stimulate further randomized trials of pirfe-nidone in patients with nonalcoholic steatohepatitis-related liver fibrosis or cirrhosis,for whom no recommended drug treatments exists currently.展开更多
基金Project supported by the National Natural Science Foundation of China No: 39670837
文摘Objective: To study the antifibrotic effects of genistein(GE) and quercetin(QU) on rat hepatic stellate HSC-T6 cell proliferation stimulated with platelet-derived growth factor (PDGF), collagen synthesis and type I procollagen messenger RNA (mRNA) expression stimulated with transforming growth factor b1 (TGFb1). Methods: Cell proliferation was measured by crystal violet staining assay. Collagen synthesis was determined by 3H-proline incorporation assay. Type I procollagen mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). Results: GE (25~70 mmolL-1) and QU (6.25~50 mmolL-1) concentration-dependently attenuated PDGF-driven HSC-T6 cell proliferative activity. TGFb1-stimulated collagen synthesis was also reduced. This was associated with a decrease in type I procollagen mRNA expression, indicating an effect at a pretranslational level. Conclusion: GE and QU may have therapeutic potential against liver fibrosis by regulating PDGF and TGFb1 actions.
文摘A variety of surgical techniques have traditionally been used to manage cicatricial ectropion. These techniques primarily aim at vertical lengthening of the anterior lamella and include a variety of skin flaps and grafts. Alternative techniques such as dermal filler injection to support the eyelid margin may also be used in the management of select patients with cicatricial ectropion. The application of different types of laser for scar revision throughout the body has rapidly evolved; similar mechanisms, principles and treatment rationale can be applied to the use of lasers in the management of cicatricial ectropion. Additionally, ablative lasers, such as Carbon Dioxide and Erbium:yttrium-aluminumgarnet lasers, may be used in the transdermal delivery of antifibrotic agents, such as interferon gamma, interferon alpha, vitamin D, triamcinolone and 5-fluorouracil, resulting in efficient target tissue penetration, limitation of systemic drug toxicity and decreased degradation. Although the combination of ablative fractional resurfacing and topical antifibrotic agents is a new treatment modality, there is a great potential for its efficient utilityin the management of periocular scarring and cicatricial ectropion. The introduction of these innovative therapeutic modalities offers ophthalmologists a greater range of possible effective treatments to address periocular scar tissue and the resultant cicatricial ectropion.
文摘Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network pharmacology.Methods:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day.In IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were measured.Histological alterations in lung tissues were also assessed.Moreover,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF.Results:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of mice.Moreover,trigonelline alleviated bleomycin-induced histological alterations in lung tissues.Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and TLR4.Conclusions:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF.It may be considered an antifibrotic agent for further clinical development.
基金Supported by National Natural Science Foundation of China,No.82172754 and No.81874208Natural Science Foundation Project of Hubei Province,No.2021CFB562.
文摘In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcohol-associated liver disease(ALD)on human health.Given its insidious onset and increasing incidence,increasing awareness of ALD can contribute to reducing the prevalence of liver diseases.ALD comprises a spectrum of several different disorders,including liver steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.The pathogenesis of ALD is exceedingly complex.Previous studies have shown that peroxisome proliferator-activated receptors(PPARs)regulate lipid metabolism,glucose homeostasis and inflammatory responses within the organism.Additionally,their dysfunction is a major contributor to the progression of ALD.Elafibranor is an oral,dual PPARαandδagonist.The effectiveness of elafibranor in the treatment of ALD remains unclear.In this letter,we emphasize the harm of ALD and the burden it places on society.Furthermore,we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets.Additionally,we discuss the mechanisms of action of PPARαandδagonists,the significance of their antifibrotic effects on ALD and future research directions.
文摘In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its impact on lung function of IPF patients.PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages.It inhibits various pathways and has antifibrotic,anti-inflammatory,and antioxidant properties.Despite dosage lowering,PFD slowed IPF progression and maintained functional capacity.The 6-min walk distance test indicated that patients tolerated adverse events well,and PFD significantly reduced the incidence of progression episodes and death.Even when a single disease-progression event occurred,continuing PFD treatment had benefits.
文摘The global incidence of nonalcoholic fatty liver disease(NAFLD)is escalating considerably.NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis,which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix,leading to fibrosis.Hepatocyte ballooning is a key catalyst for fibrosis progression,potentially advancing to cirrhosis and its decompensated state.Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD;therefore,those with substantial fibrosis require timely intervention.Although liver biopsy is the most reliable method for fibrosis detection,it is associated with certain risks and limitations,particularly in routine screening.Consequently,various noninvasive diagnostic techniques have been introduced.This review examines the increasing prevalence of NAFLD,evaluates the noninvasive diagnostic techniques for fibrosis,and assesses their efficacy in staging the disease.In addition,it critically appraises current and emerging antifibrotic therapies,focusing on their mechanisms,efficacy,and potential in reversing fibrosis.This review underscores the urgent need for effective therapeutic strategies,given the dire consequences of advanced fibrosis.
基金Tianjin Science and Technol-ogy Project (15ZXLCSY00040)
文摘The incidence rate and mortality of liver fibrosis caused by various etiologies are high throughout the world. Liver fibrosis, the subsequent cirrhosis and other serious related complications threaten the health of patients and represent a serious medical burden;yet, there is still a lack of approved methods to prevent or reverse liver fibrosis. Therefore, effective hepatic antifibrotic drugs are urgently needed. The activation and proliferation of hepatic stellate cells are still the mechanisms of fibrosis that remain the focus of therapeutic research. In recent years, significant progress has been made in the development and applicability of antifibrosis drugs. In this review, we summarize the effectiveness and safety of available antifibrosis drugs utilizing different targets. In addition, some characteristics of antifibrosis drugs in phase II and III trials are introduced in detail.
基金funded by grant from Croatian Ministry of Science and Education dedicated to multi-year institutional funding of scientific activity at the J.J.Strossmayer University of Osijek,Osijek,Croatia—grant number:IP6-MEFOS-2019(to R.S.).
文摘Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing incidence.Therefore,there is a great impetus for development of agents targeting these conditions.Accumulating data on possible treatment options for liver fibrosis are emerging in the literature.However,despite extensive research and much effort in the field,approved agents for liver fibrosis are still lacking.In this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.
文摘Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease(the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.
基金Supported by Grants from the Italian Ministero dell’Istruzione,dell’Universitàe della Ricerca(Ministry for Education,Universities and Research),MIUR FIRB-MERIT n.RBNE08YYBM to Cervello M,Montalto G and BondìML
文摘Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and,in the more advanced stages,for the limited available curative treatment options.In fact,when lesions of different etiologies chronically affect the liver,triggering the fibrogenesis mechanisms,damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications,expensive treatments and death in end-stage liver disease.Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis,the drugs used in liver fibrosis treatment still have a limited therapeutic effect.Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected.Hepatic stellate cells play a critical role in liver fibrogenesis,thus they are the target cells of antifibrotic therapy.The application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents(including drugs and nucleic acid)in the treatment of various pathologies,including liver disease.In this review,we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.
基金Supported by Research grant from key clinical disciplines construction of Shanghai Municipality,China,No.ZK2012B20
文摘Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix(ECM) accumulation and degradation. The relentlessproduction and progressive accumulation of ECM can lead to end-stage liver disease. Although significant progress has been achieved in elucidating the mechanisms of fibrogenesis, effective anti-fibrotic strategies are still lacking. Autophagy is an intracellular process of self-digestion of defective organelles to provide material recycling or energy for cell survival. Autophagy has been implicated in the pathophysiology of many human disorders including hepatic fibrosis. However, the exact relationships between autophagy and hepatic fibrosis are not totally clear and need further investigations. A new therapeutic target for liver fibrosis could be developed with a better understanding of autophagy.
基金supported by the National Natural Science Foundation of China(No.32170403)the 111 Center from Ministry of Education of China and the State Administration of Foreign Experts Affairs of China(No.B18056)+1 种基金the“Double First-Class”University Project(No.CPU2018GF03)the Drug Innovation Major Project(Nos.2018ZX09711-001-007 and 2018ZX09735002-003)。
文摘Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction analysis.Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers.Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides.In addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.
基金Supported by the Research Foundation in Combination of TCM with Western Medicine under the Natural Science Foundation of Suzhou Scitech Bureau (SYSD2011148)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)the grant from the emphasis course of study & "211" projectof Soochow University (No. 14317336)
文摘OBJECTIVE: The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we applied randomly controlled trial to check the curative effect of Chinese herbs on patients with immunoglobulin A nephropathy (IgAN). METHODS: Twenty-six patients were randomly divided into group A (control group) treated with Western Medicine and group B (treatment group) treated with combination of Traditional Chinese Medicine (TCM) and Western Medicine. Blood and urine tests were done before treatment and after 8-week treatment. RESULTS: The levels of the main composition of ex- tracellular matrix (MC-ECM), the metabolic enzyme of ECM (ME-ECM) and some cytokines in group B decreased more obviously than those in group A after 8-week treatment. So did the level of 24-hour urine protein. However, Metal matrix protease (MMP)-2 and vascular endothelial growth factor in group B increased more obviously than those in group A after 8-week treatment. No effects on the renal function were found in both groups. CONCLUSION: Our study provided important information on using the combination of TCM with Western Medicine to inhibit the progression of renal fibrosis in patients with IgAN.
文摘We repurposed the antifibrotic drug pirfenidone—which is approved for treatment of idiopathic lung fibrosis—in a series of patients with nonalcoholic steatohepatitis-related cirrhosis.Our report demonstrates the observed improvements in necroinflammation and regression of cirrhosis with pirfeni-done use for 12-weeks,associated with classical hepatic repair complex features on follow-up liver biopsies.This novel work could help stimulate further randomized trials of pirfe-nidone in patients with nonalcoholic steatohepatitis-related liver fibrosis or cirrhosis,for whom no recommended drug treatments exists currently.
