Malignant mesothelioma is a highly aggressive cancer with poor prognosis and refractory to currently available therapies. Most of the patients with advanced invasive nature are not amenable to surgical resection and/or available anticancer therapy, thus development of novel effective therapeutic regimes is needed. Aberrant expression of microRNAs (miRNAs) has been proposed to contribute to carcinogenesis and aggressiveness of mesothelioma. We analyzed miRNA expression in mesothelioma cell lines using TaqMan miRNA expression array and found significant number of miRNAs, which showed increased or lost expression. We validated the increased expression of miR-182, and miR-183 in mesothelioma cell lines by individual miRNA assays and SmartFlare miRNA probes. We further investigated the miR-1, and miR-214, which were not expressed in mesothelioma cells by real-time RT-PCR. Transfection of mesothelioma cells, ACC-Meso-1 and CRL5915, with miRNA mimic (hsa-miR-1 mimic and hsa-miR-214 mimic) led to inhibition of cell growth, invasion and migration. We paid attention to PIM1, the target gene of both miR-1 and miR-214 miRNAs and which was found overexpressed in mesothelioma cells, and miR-1 and miR-214 mimic transfection of mesothelioma cell lines showed downregulation of PIM1 by western blot analysis. The miRNAs, miR-1 and miR-214, may play a role in carcinogenesis of mesothelioma thus might be considered as candidate therapeutic targets in mesothelioma.

Objectives: This study aimed to evaluate the role of platelet rich plasma (PRP) in the treatment of lung fibrosis induced by amiodarone drug. Materials and Methods: Seventy adult male Wistar albino rats were divided into three groups (n=20) plus ten rats were used for PRP collection. The first group used as control group. The rats in second group (gp.2) were injected intraperitoneally (i.p.) daily with amiodarone drug at (80 mg/ kg. bwt) for three weeks, then injected (24 hours after last dose of amiodarone) (i.p.) with phosphate buffer saline (PBS) (0.5 ml/ kg. bwt) two times weekly for three weeks. The rats in third group (gp.3) were injected (i.p.) daily with amiodarone drug at (80 mg/ kg. bwt) for three weeks, plus (i.p.) injection with platelet rich plasma (PRP) at dose (0.5 ml/kg. bwt) (24 hours after last dose of amiodarone injection) two times weekly for three weeks. The animals were examined during the experiment and sacrificed at the end of the experiment. Results: Rats in the PRP treatment (gp. 3) showed an increase in the level of WBCs and RBCs counts in comparison with group 2. Significant increase in glutathione reductase and a significant decrease in malondialdehyde levels were detected in group 3 when compared with group 2. The histopathological findings showed an improvement in the fibrosed lungs compared to gp (2). Conclusions: This study concluded the remodeling effect of PRP, which was observed clinically and pathologically against the harmful effects of amiodarone in albino rats.

BackgroundLambda-cyhalothrin (LTC) is a synthetic pyrethroid insecticide for agricultural and public health applications. This study was to determine the pathological alterations of LTC in lungs, which has not previously been studied, and the ameliorating effects of plant extracts (ginseng and garlic) on the development of asthma in albino rats.MethodsFour groups (gps) of albino rats, (n = 20, average body weight = 200 gm with an age of 4 months), were formed. Gp 1 was kept as control. Gp 2 was injected intraperitoneally (i.p.) with LTC at a dose of 1/6 LD50 that is 9.34 mg/kg body weight (w.t.) daily for 21 days (d). Gp 3 & 4 were injected (i.p.) with ginseng at the dose of 200 mg/kg b.wt and garlic (Allium sativum L.) at the dose of 100 mg/kg b.wt., respectively, one hour before being given LTC at a dose of 1/6 LD50 (9.34 mg/kg b.wt.) daily. Each groups were divided into two sacrificed, at 15 and 21 d p.i. Blood and lung samples were collected for hematological and histopathological examinations.ResultsHematological findings showed that the animals in gps 2 and 3, which were treated for 21 days, showed a significant difference in RBC counts (P > .001), Hb (P > .007), PCV% (P > .004), (P > .008) in comparison with the control group. Signs of cough and nasal discharge were seen in gp 2, which became mild in gp 4. Grossly, the lungs showed congestion and consolidation in gp 2. Histopathologically, macroabscesses and interstitial alveolitis were seen in gp 2, which led to obstruction in the lumen of the bronchioles at 21 d p.i. Meanwhile, thickening in the interalveolar septa with mononuclear cells was seen in gps. 3 and 4 at 21d p.i.ConclusionsThe study shows 3 gps of rats injected with LHC alone or combined with garlic and ginseng extract, each group were divided into two sacrificed (15 and 21 d p.i.). Lambda cyhalothrin causes bronchial obstruction in the lungs of the rats (15 and 21 d p.i), which decreased into mild to moderate interstitial inflammation in the rats given garlic and ginseng, respectively.

Malignant mesothelioma is a major asbestos-related cancer with prolonged time lapse from the first exposure of asbestos to the development of mesothelioma. Most of mesothelioma patients show very poor prognosis, thus, an urgent improvement of its treatment is required by development of novel therapeutic strategies. RNA interference (RNAi) is a powerful tool in post-genomic research and cancer therapy through inhibition of gene expression. In the present study, we analyzed the function of PIM1 on mesothelioma cell lines with its knockdown by siRNA transfection. Here, we report that the downregulation of PIM1 led to suppression of cell proliferation by cell cycle arrest at G1 phase and suppression of cell invasion and migration. Considering the mesothelioma as rapidly growing invasive cancer, downregulation of PIM1 may have a potential role for therapeutic management of malignant mesothelioma.

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