AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis.

The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated.

Pirfenidone Protects from UVB-Induced Photodamage in Hairless Mice.

Background: Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized.

Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the sixth most frequent cancer in the world, being the third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) is characterized by fatty infiltration, oxidative stress and necroinflammation of the liver, with or without fibrosis, which can progress to advanced liver fibrosis, cirrhosis and HCC. Obesity, metabolic syndrome, insulin resistance, and diabetes exacerbates the course of NASH, which elevate the risk of HCC.

Hepatocarcinogenesis Prevention by Pirfenidone Is PPARγ Mediated and Involves Modification of Nuclear NF-kB p65/p50 Ratio.

Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPARγ expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process.

Liver Cancer: Therapeutic Challenges and the Importance of Experimental Models.

Liver cancer is one of the main causes of death related to cancer worldwide; its etiology is related with infections by C or B hepatitis virus, alcohol consumption, smoking, obesity, nonalcoholic fatty liver disease, diabetes, and iron overload, among other causes. Several kinds of primary liver cancer occur, but we will focus on hepatocellular carcinoma (HCC). Numerous cellular signaling pathways are implicated in hepatocarcinogenesis, including YAP-HIPPO, Wnt--catenin, and nuclear factor-B (NF-B); these in turn are considered novel therapeutic targets.

Roles of Nrf2 in Liver Diseases: Molecular, Pharmacological, and Epigenetic Aspects.

Liver diseases represent a critical health problem with 2 million deaths worldwide per year, mainly due to cirrhosis and its complications. Oxidative stress plays an important role in the development of liver diseases. In order to maintain an adequate homeostasis, there must be a balance between free radicals and antioxidant mediators.

Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial.

Background: Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent.

Role and New Insights of Pirfenidone in Fibrotic Diseases.

Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-β1, TNF-α, PDGF and COL1A1 expression, which is highly related to prevent or remove excessive deposition of scar tissue in several organs. Basic and clinical evidence suggests that PFD may safely slow or inhibit the progressive fibrosis swelling after tissue injuries. Furthermore, a number of evidence suggests that this molecule will have positive effects in the treatment of other inflammatory diseases.

Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C.

Background: The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-β1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC).

Methods: Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD.

Controlled clinical trial with pirfenidone in the treatment of breast capsular contracture: association of TGF-β polymorphisms.

Background: Breast capsular contracture (BCC) is a commonly adverse event postmammoplastly characterized by an immune response mediated by cytokines and transforming growth factor (TGF)-β1 resulting in excessive synthesis and deposit of extracellular matrix around the breast implant. Presence of TGF-β1 polymorphisms has been associated as a risk factor to develop fibroproliferative diseases.

Methods: This open, controlled, prospective, and pilot clinical trial with 6 months duration was carried out to evaluate the efficacy of 1800 mg a day, of oral Pirfenidone (PFD) in the treatment of BCC (Baker Score III/IV) postmammoplasty.

Adenoviral delivery of dominant-negative transforming growth factor beta type II receptor up-regulates transcriptional repressor SKI-like oncogene, decreases matrix metalloproteinase 2 in hepatic stellate cell and prevents liver fibrosis in rats.

Background: Dominant-negative transforming growth factor beta type II receptor (TbetaRIIDeltacyt) is a protein that blocks transforming growth factor (TGF-beta) signaling. Because the consequences of blocking TGF-beta have not been completely elucidated in liver fibrosis, we analysed the effects of adenoviral delivery of TbetaRIIDeltacyt on profibrogenic genes and matrix metalloproteinase (MMP) proteins, as well as on TGF-beta signal repressor SKI-like oncogene (SnoN), in cultured hepatic stellate cells (HSCs) and in a rat model of liver fibrosis.

Methods: To induce liver fibrosis, rats were treated with thioacetamide for 7 weeks and administrated once with Ad-TbetaRIIDeltacyt or Ad-betagal through the iliac vein.