Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5–10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKKα-β/NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

(2013). Caffeic acid protects tissue antioxidants and DNA content in methamphetamine induced tissue toxicity in Sprague Dawley rats. Toxicology Mechanisms and Methods: Vol. 23, No. 2, pp. 134-143.

In schistosomiasis, the host/parasite interaction remains not completely understood. Many questions related to the susceptibility of snails to infection by respective trematode still remain unanswered. The control of schistosomiasis requires a good understanding of the host/parasite association. In this work, the susceptibility/resistance to Schistosoma mansoni infection within Biomphalaria alexandrina snails were studied starting one month post infection and continuing thereafter weekly up to 10 weeks after miracidia exposure. Genetic variations between susceptible and resistant strains to Schistosoma infection within B. alexandrina snails using random amplified polymorphic DNA analysis technique were also carried out. The results showed that 39.8% of the examined field snails were resistant, while 60.2% of these snails showed high infection rates.In the resistant genotype snails, OPA-02 primer produced a major low molecular weight marker 430 bp. Among the two snail strains there were interpopulational variations, while the individual specimens from the same snail strain, either susceptible or resistant, record semi-identical genetic bands. Also, the resistant character was ascendant in contrast to a decline in the susceptibility of snails from one generation to the next.

To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of (1)H NMR-spectrometry. The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with (1)H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database, Chenomx Profiler. The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions; infected with dengue. Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle. The (1)H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures, gave an evidence for the existence of distinct metabolic differentiation of individuals, according to their gender, modulates with the infection risk.