Cyclic peptides nanospheres: A '2-in-1' self-assembled delivery system for targeting nucleus and cytoplasm.

Vascular endothelial growth factor (VEGF) is considered as one of the vital growth factors for angiogenesis, which is primarily responsible for the progress and maintenance of new vascular network in tumor. Numerous studies report that inhibition of VEGF-induced angiogenesis is a potent technique for cancer suppression. Recently, RNA interference, especially small interfering RNA (siRNA) signified a promising approach to suppress the gene expression. However, the clinical implementation of biological macromolecules such as siRNA is significantly limited because of stability and bioavailability issues. Herein, self-assembled peptide nanospheres have been generated from L,L-cyclic peptides using hydrophobic (Trp), positively charged (Arg) and cysteine (Cys) amino acid residues and demonstrated as vehicles for intracellular delivery of VEGF siRNA and VEGF antisense oligonucleotide. Formation of peptide nanostructures is confirmed by HR-TEM, AFM, SEM and DLS analysis. Possible mechanism of self-assembly of the cyclic peptides and their binding with macromolecules are demonstrated by in-silico analysis. Gel electrophoresis reveals that the newly generated peptide based organic materials exhibit strong binding affinity toward siRNAs / antisense oligonucleotides (ASOs) at optimum concentration. Flow cytometry and confocal microscopy results confirm the efficiency of the new biomaterials toward the intracellular delivery of fluorescent labeled siRNA / ASOs. Furthermore, VEGF expression evaluated by western blot and RT-PCR upon the delivery of functional VEGF siRNA/ASOs suggests that very low concentrations of VEGF siRNA/ASOs cause significant gene knockdown at protein and mRNA levels, respectively.

Carbon nano-dot for cancer studies as dual nano-sensor for imaging intracellular temperature or pH variation.

Cellular temperature and pH govern many cellular physiologies, especially of cancer cells. Besides, attaining higher cellular temperature plays key role in therapeutic efficacy of hyperthermia treatment of cancer. This requires bio-compatible, non-toxic and sensitive probe with dual sensing ability to detect temperature and pH variations. In this regard, fluorescence based nano-sensors for cancer studies play an important role. Therefore, a facile green synthesis of orange carbon nano-dots (CND) with high quantum yield of 90% was achieved and its application as dual nano-sensor for imaging intracellular temperature and pH was explored. CND was synthesized from readily available, bio-compatible citric acid and rhodamine 6G hydrazide using solvent-free and simple heating technique requiring purification by dialysis. Although the particle size of 19 nm (which is quite large for CND) was observed yet CND exhibits no surface defects leading to decrease in photoluminescence (PL). On the contrary, very high fluorescence was observed along with good photo-stability. Temperature and pH dependent fluorescence studies show linearity in fluorescence intensity which was replicated in breast cancer cells. In addition, molecular nature of PL of CND was established using pH dependent fluorescence study. Together, the current investigation showed synthesis of highly fluorescent orange CND, which acts as a sensitive bio-imaging probe: an optical nano-thermal or nano-pH sensor for cancer-related studies.

Intussusception in children aged under two years in India: Retrospective surveillance at nineteen tertiary care hospitals.

OBJECTIVE: Intussusception has been linked with rotavirus vaccine (RVV) as a rare adverse reaction. In view of limited background data on intussusception in India and in preparation for RVV introduction, a surveillance network was established to document the epidemiology of intussusception cases in Indian children. METHODS: Intussusception in children 2-23 months were documented at 19 nationally representative sentinel hospitals through a retrospective surveillance for 69 months (July 2010 to March 2016). For each case clinical, hospital course, treatment and outcome data were collected. RESULTS: Among the 1588 intussusception cases, 54.5% were from South India and 66.3% were boys. The median age was 8 months (IQR 6, 12) with 34.6% aged 2-6 months. Seasonal variation with higher cases were documented during March-June period. The most common symptoms and signs were vomiting (63.4%), bloody stool (49.1%), abdominal pain (46.9%) and excessive crying (42.8%). The classical triad (vomiting, abdominal pain, and blood in stools) was observed in 25.6% cases. 96.4% cases were diagnosed by ultrasound with ileocolic location as the commonest (85.3%). Management was done by reduction (50.8%) and surgery (41.1%) and only 1% of the patients' died. 91.1% cases met Brighton criteria level 1 and 3.3% Level 2. Between 2010 and 2015, the case load and case ratio increased across all regions. CONCLUSION: Intussusception cases have occurred in children across all parts of the country, with low case fatality in the settings studied. The progressive rise cases could indicate an increasing awareness and availability of diagnostic facilities.

Synthesis and extraction studies with a rationally designed diamide ligand selective to actinide(iv) pertinent to the plutonium uranium redox extraction process.

A new class of conformationally constrained oxa-bridged tricyclo-dicarboxamide (OTDA) ligand was rationally designed for the selective extraction of tetravalent actinides pertinent to the Plutonium Uranium Redox EXtraction (PUREX) process. Two of the designed diamide ligands were synthesized and extraction studies were performed for Pu(iv) from HNO3 medium. The mechanism of extraction was investigated by studying various parameters such as feed HNO3, NaNO3 and OTDA concentrations. The nature of the extracted species was found to be [Pu(NO3)4(OTDA)]. One of the OTDA ligands was elaborately tested and showed the selective extraction of Pu(iv) and Np(iv) over other actinide species, viz., U(vi), Np(v), Am(iii), lanthanides and fission products contained in a nuclear waste from the PUREX process. DFT calculations predicted the charge density on each of the coordinating 'O' atoms of OTDA supporting its high Pu(iv) selectivity over other ions studied and also provided the energy optimized structure of OTDA and its Pu(iv) complex.

Resveratrol metabolites do not elicit early pro-apoptotic mechanisms in neuroblastoma cells.

Resveratrol, a nontoxic polyphenol, has been shown to inhibit tumor growth in a xenograft mouse model of neuroblasoma. However, resveratrol is rapidly metabolized, mainly to its glucuronidated and sulfated derivatives. This study demonstrates that resveratrol alone, and not the glucuronidated or sulfated metabolites, is taken up into tumor cells, induces a rise in [Ca(2+)](i), and ultimately leads to a decrease in tumor cell viability. A new water-soluble resveratrol formulation was delivered directly at the site of the tumor in a neuroblastoma mouse model. The amount of unmodified resveratrol associated with the tumor increased more than 1000-fold. The increase of unmodified resveratrol associated with the tumor resulted in tumor regression. The number of residual tumor cells that remained viable also decreased as the ratio of the metabolites relative to unmodified resveratrol declined.