Gelatinases Increase in Bleomycin-induced Systemic Sclerosis Mouse Model

Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma

The role of progesterone in cellular apoptosis of skin and lung in a bleomycin-injured mouse model

Systemic sclerosis is a female predominant, a fibrotic autoimmune disease in which disturbance in tissue homeostasis and cell turnover including cell apoptosis are central events in pathogenesis. Sex hormones are known as the important players in sexual dimorphism of autoimmune diseases and in tissue homeostasis. Progesterone influences autoimmune disease via its immunomodulatory effect or by its direct action on parenchymal cell function. On the other hand, this hormone impacts tissue homeostasis by acting on cell apoptosis in a different situation. The objective of this study was to examine the effect of progesterone on cellular apoptosis of skin and lung tissues in a mouse model of scleroderma. Four group of mice were involved in this study with 10 mice in each. The fibrotic model was induced by daily subcutaneous injection of bleomycin for 28 days. One week after initiation of fibrosis induction, mice received subcutaneous progesterone alone or with bleomycin for 21 days. Control group received only Phosphate buffered saline PBS. After 28 days, under lethal anesthesia skin and lung tissues were harvested for histological assessment and hydroxyproline measurement. Apoptosis in tissue sections was detected by TUNEL assay technique. Bleomycin administration induced fibrosis in skin and lung tissues. Severe apoptosis was seen in skin and lung tissues of the bleomycin-treated group (p0.05) or in the lung (p>0.05) did not alter apoptosis in bleomycin-treated animals. Our data confirm the role of apoptosis in the pathogenesis of fibrosis in this model; however, progesterone does not affect cellular apoptosis in skin and lung tissues of bleomycin-injured animals. Copyright© February 2019, Iran J Allergy Asthma Immunol. All rights reserved

In vitro anti-cancer efficacy of multi-functionalized magnetite nanoparticles combining alternating magnetic hyperthermia in glioblastoma cancer cells

Localized hyperthermia and the targeted release of the chemotherapy drug are one of the most challenging problems in chemo-hyperthermia therapy. In the present study, magnetite nanoparticles as a carrier of Temozolomide (TMZ) functionalized with folic acid-ligand (TMZ-MNP-FA) were designed and developed for targeted chemotherapy and radiofrequency hyperthermia of cancer cells. Nanoparticles were synthesized and characterized for hydrodynamic diameter, zeta potential, morphology, drug loading capacity, and in vitro RF-triggered release. Their cytotoxicity and efficacy as targeted drug delivery systems were evaluated in both cancer and normal cells and the therapeutic efficacy was analyzed on the C6 glioblastoma cancer cells. The C6 cells were treated with the nanoparticles and subjected to an alternating magnetic field (AMF) to reach a typical hyperthermia temperature of 43 °C. Then induction of apoptotic cells and the proliferation capacity of cancer cells were evaluated. The in vitro release studies exhibited that the drug release from TMZ-loaded magnetite nanoparticles was minimal at 37 °C but was noticeably boosted under an AMF irradiation. The developed targeted magnetite nanoparticles revealed higher cytotoxic effect and cellular uptake in folate-receptor overexpressing C6 cancer cells compared to OLN-93 normal cells. All results showed that combined magnetite chemo-hyperthermia (AMF + TMZ-MNP-FA) treatment was significantly more efficacious in cancer cells than hyperthermia, chemotherapy, or chemo-hyperthermia treatments (P < 0.0001). In conclusion, TMZ-MNP-FA had a key role to convert the externally delivered radiofrequency energy to heat in cancer cells. Additionally, localized hyperthermia triggered a TMZ release from the nanocarriers that resulted in cancer cell damage with synchronizing hyperthermia and chemotherapy. © 2019 Elsevier B.V