METHODS: Pre-differentiation of eGFP-expressing AFMSCs to lung epithelial progenitor-like cells (LEPLCs) was established under a modified small airway growth media (mSAGM) for 7-day induction. Pre-differentiated AFMSCs were intratracheally injected into porcine pancreatic elastase (PPE)-induced emphysema mice at day 14, and then inflammatory-, fibrotic-, and emphysema-related indices and pathological changes were assessed at 6 weeks after PPE administration.

RESULTS: An optimal LEPLCs pre-differentiation condition has been achieved, which resulted in a yield of approximately 20% lung epithelial progenitors-like cells from AFMSCs in a 7-day period. In PPE-induced emphysema mice, transplantation of LEPLCs significantly improved regeneration of lung tissues through integrating into the lung alveolar structure, relieved airway inflammation, increased expression of growth factors such as vascular endothelial growth factor (VEGF), and reduced matrix metalloproteinases and lung remodeling factors when compared with mice injected with AFMSCs. Histopathologic examination observed a significant amelioration in DNA damage in alveolar cells, detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), the mean linear intercept, and the collagen deposition in the LEPLC-transplanted groups.

MATERIALS AND METHODS: In this study, we focus on two important drugs used for TB treatment - rifampicin (RIF) and isoniazid (INH) - and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions.

RESULTS: It was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL).

RESULTS: The dichloromethane extract of P. crispum exhibited the highest phenolic content (42.31 ± 0.50 mg GAE g(-1) ) and ferric reducing ability (0.360 ± 0.009 mmol g(-1) ) of the various extractions performed. The extract showed DPPH radical scavenging activity with an IC50 value of 3310.0 ± 80.5 µg mL(-1) . Mouse fibroblasts (3T3-L1) pre-treated with 400 µg mL(-1) of the extract showed 50.9% protection against H2 O2 -induced DNA damage, suggesting its potential in cancer prevention. The extract (300 µg mL(-1) ) inhibited H2 O2 -induced MCF-7 cell migration by 41% ± 4%. As cell migration is necessary for metastasis of cancer cells, inhibition of migration is an indication of protection against metastasis.

METHODOLOGY/PRINCIPAL FINDINGS: The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells (IC50, 34 ± 3.52 and 32.42 ± 0.37 μg/ml, respectively). Oxidative stress due to disruption of antioxidant enzyme (SOD, GPx and CAT) activity is suggested as the probable cause for apoptosis initiation. Though the main apoptosis pathway in both cell lines was found to be through caspase-8 activation, caspase-9 was also activated in MDA-MB-231 cells but suppressed in MCF-7 cells. Gene expression studies revealed that AKT1, the caspase-9 suppressor, was up-regulated in MCF-7 cells while down-regulated in MDA-MB-231 cells. Although, AKT1 protein expression in both cell lines was down-regulated, a steady increase in MCF-7 cells was observed after a sharp decrease of suppression of AKT1. Trans-cinnamaldehyde and coumarin were isolated and identified and found to be mainly responsible for the observed anti-proliferative activity of CE (Cinnamomum cassia).