METHODS: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body.
RESULTS: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation.
CONCLUSION: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.
PURPOSE: For the first time, our study aims to demonstrate the molecular mechanisms of the fruit extract of Phyllanthus emblica (PEFE) involved in the promotion of fat cell apoptosis and alleviation of adipogenesis.
METHODS: The active constituents from PEFE were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). We carried out the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects of PEFE using 3T3-L1 pre-adipocytes. The colonogenic assay was carried out to determine the inhibitory effect of 3T3-L1 adipocytes after PEFE treatment. In addition, inhibition of pancreatic lipase activity was performed and the lipolytic activity of PEFE and digallic acid was compared with the well-known standard drug orlistat. Besides, the molecular interaction and ligand optimization between digallic and adipogenesis/apoptosis markers were also carried out. Furthermore, to confirm fat cell apoptosis we have used several detection methods that includes Hoechst staining, PI staining, Oil staining and qPCR respectively.
RESULTS: Digallic acid was identified as a major component in the PEFE. The IC50 values of digallic acid and PEFE were found to be 3.82 µg/ml and 21.85 µg/ml respectively. PEFE and digallic acid showed significant anti-lipolytic activity compared to the standard drug orlistat. In the mature adipocytes, PEFE significantly decreased triglyceride accumulation by downregulating adiponectin, PPARγ, cEBPα, and FABP4 respectively. We further analyzed the expression of apoptosis related genes upon PEFE treatment. Apoptotic process initiated through upregulation of BAX and downregulation of BCL2 resulting in an increased caspase-3 activity. In addition, we have also confirmed the apoptosis and DNA fragmentation in 3T3-L1 cells using Hoechst, PI and TUNEL assays.
CONCLUSION: PEFE negatively regulates adipogenesis by initiating fat cell apoptosis and therefore it can be considered as a potential herbal medicinal product for treating obesity.
METHODS: In a double blind, randomised crossover design, 12 well-trained male runners completed 4 running time to exhaustion (TTE) trials at a speed equivalent to 70% of VO2peak in a thermoneutral condition. Throughout each run, participants mouth rinsed and expectorated every 15 min either 25 mL of 6% CHO or a placebo (PLA) solution for 10 s. The four TTEs consisted of two trials in the euhydrated (EU-CHO and EU-PLA) and two trials in the dehydrated (DY-CHO and DY-PLA) state. Prior to each TTE run, participants were dehydrated via exercise and allowed a passive rest period during which they were fed and either rehydrated equivalent to their body mass deficit (i.e., EU trials) or ingested only 50 mL of water (DY trials).
RESULTS: CHO mouth rinsing significantly improved TTE performance in the DY compared to the EU trials (78.2 ± 4.3 vs. 76.9 ± 3.8 min, P = 0.02). The arousal level of the runners was significantly higher in the DY compared to the EU trials (P = 0.02). There was no significant difference among trials in heart rate, plasma glucose and lactate, and psychological measures.
CONCLUSIONS: CHO mouth rinsing enhanced running performance significantly more when participants were dehydrated vs. euhydrated due to the greater sensitivity of oral receptors related to thirst and central mediated activation. These results show that level of dehydration alters the effect of brain perception with presence of CHO.