Metabolomic Approaches in Cancer Epidemiology

Metabolomics is the study of low molecular weight molecules or metabolites produced within cells and biological systems. It involves technologies such as mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) that can measure hundreds of thousands of unique chemical entities (UCEs). The metabolome provides one of the most accurate reflections of cellular activity at the functional level and can be leveraged to discern mechanistic information during normal and disease states. The advantages of metabolomics over other “omics” include its high sensitivity and ability to enable the analysis of relatively few metabolites compared with the number of genes and messenger RNAs (mRNAs). In clinical samples, metabolites are more stable than proteins or RNA. In fact, metabolomic profiling in basic, epidemiologic, clinical, and translational studies has revealed potential new biomarkers of disease and therapeutic outcome and has led to a novel mechanistic understanding of pathogenesis. These potential biomarkers include novel metabolites associated with cancer initiation, regression, and recurrence. Unlike genomics or even proteomics, however, the degree of metabolite complexity and heterogeneity within biological systems presents unique challenges that require specialized skills and resources to overcome. This article discusses epidemiologic studies of altered metabolite profiles in several cancers as well as challenges in the field and potential approaches to overcoming them

Newly designed resorcinolate binding for Ru(II)– and Re(I)–polypyridyl complexes on oleic acid capped TiO₂ in nonaqueous solvent: prolonged charge separation and substantial thermalized ³MLCT injection

Femtosecond pump–probe spectroscopic studies on a series of newly synthesized resorcinol-based Ru(II) and Re(I) complexes on oleic acid capped TiO2 nanoparticles have been carried out in chloroform, and the results are compared with those of the catechol analogues. The ruthenium complex shows biexponential injection; the second component arises due to injection from the thermally equilibrated 3MLCT states as a result of a weaker strength of the resorcinolate binding. Also, in comparison with catechol binding, as a result of a greater diffusion of the injected electrons into TiO2 , the back electron transfer (BET) is slowed down significantly for the ruthenium complex. These are distinctive observations for any mononuclear ruthenium–polypyridyl–enediol complex reported thus far. However, the rhenium complex educes single exponential ultrafast injection (<120 fs) because of apparent injection in a high density of states and shows the most prominent results with ∼50% slowdown in the charge recombination rate as compared to the analogous catechol bound system. These results exemplify the probable development of highly capable sensitizer dyes with resorcinol as the anchoring group for the development of efficient dye-sensitized solar cells

Synthesis, steady-state, and femtosecond transient absorption studies of resorcinol bound ruthenium(II)- and osmium(II)-polypyridyl complexes on nano-TiO₂ surface in water

The synthesis of two new ruthenium(II)- and osmium(II)-polypyridyl complexes 3 and 4, respectively, with resorcinol as the enediol anchoring moiety, is described. Steady-state photochemical and electrochemical studies of the two sensitizer dyes confirm strong binding of the dyes to TiO₂ in water. Femtosecond transient absorption studies have been carried out on the dye–TiO2 systems in water to reveal <120 fs and 1.5 ps electron injection times along with 30% slower back electron transfer time for the ruthenium complex 3. However, the corresponding osmium complex 4 shows strikingly different behavior for which only a <120 fs ultrafast injection is observed. Most remarkably, the back electron transfer is faster as compared to the corresponding catechol analogue of the dye. The origin and the consequences of such profound effects on the ultrafast interfacial dynamics are discussed. This Article on the electron transfer dynamics of the aforesaid systems reinforces the possibility of resorcinol being explored and developed as an extremely efficient binding moiety for use in dye-sensitized solar cells

Human Papilloma Virus-Associated Cervical Cancer and Health Disparities

Cervical cancer develops through persistent infection with high-risk human papilloma virus (hrHPV) and is a leading cause of death among women worldwide and in the United States. Periodic surveillance through hrHPV and Pap smear-based testing has remarkably reduced cervical cancer incidence worldwide and in the USA. However, considerable discordance in the occurrence and outcome of cervical cancer in various populations exists. Lack of adequate health insurance appears to act as a major socioeconomic burden for obtaining cervical cancer preventive screening in a timely manner, which results in disparate cervical cancer incidence. On the other hand, cervical cancer is aggressive and often detected in advanced stages, including African American and Hispanic/Latina women. In this context, our knowledge of the underlying molecular mechanism and genetic basis behind the disparate cervical cancer outcome is limited. In this review, we shed light on our current understanding and knowledge of racially disparate outcomes in cervical cancer

Synthesis, Steady-State, and Femtosecond Transient Absorption Studies of Resorcinol Bound Ruthenium(II)- and Osmium(II)-polypyridyl Complexes on Nano-TiO₂ Surface in Water

The synthesis of two new ruthenium­(II)- and osmium­(II)-polypyridyl complexes <b>3</b> and <b>4</b>, respectively, with resorcinol as the enediol anchoring moiety, is described. Steady-state photochemical and electrochemical studies of the two sensitizer dyes confirm strong binding of the dyes to TiO₂ in water. Femtosecond transient absorption studies have been carried out on the dye–TiO₂ systems in water to reveal <120 fs and 1.5 ps electron injection times along with 30% slower back electron transfer time for the ruthenium complex <b>3</b>. However, the corresponding osmium complex <b>4</b> shows strikingly different behavior for which only a <120 fs ultrafast injection is observed. Most remarkably, the back electron transfer is faster as compared to the corresponding catechol analogue of the dye. The origin and the consequences of such profound effects on the ultrafast interfacial dynamics are discussed. This Article on the electron transfer dynamics of the aforesaid systems reinforces the possibility of resorcinol being explored and developed as an extremely efficient binding moiety for use in dye-sensitized solar cells

New Ru(II)/Os(II)-polypyridyl complexes for coupling to TiO₂ surfaces through acetylacetone functionality and studies on interfacial electron-transfer dynamics

New Ru(II)- and Os(II)-polypyridyl complexes have been synthesized with pendant acetylacetone (acac) functionality for anchoring on nanoparticulate TiO₂ surfaces with a goal of developing an alternate sensitizer that could be utilized for designing an efficient dye-sensitized solar cell (DSSC). Time-resolved transient absorption spectroscopic studies in the femtosecond time domain have been carried out. The charge recombination rates are observed to be very slow, compared with those for strongly coupled dye molecules having catechol as the anchoring functionality. The results of such studies reveal that electron-injection rates from the metal complex-based LUMO to the conduction band of TiO₂ are faster than one would expect for an analogous complex in which the chromophoric core and the anchoring moiety are separated with multiple saturated C–C linkages. Such an observation is rationalized based on computational studies, and a relatively smaller spatial distance between the dye LUMO and the TiO₂ surface accounted for this. Results of this study are compared with those for analogous complexes having a gem-dicarboxy group as the anchoring functionality for covalent binding to the TiO₂ surface to compare the role of binding functionalities on electron-transfer dynamics

Superior grafting and state-of-the-art interfacial electron transfer rates for newly designed geminal dicarboxylate bound ruthenium(II)– and osmium(II)–polypyridyl dyes on TiO₂ nanosurface

Two new Ru(II)–/Os(II)–polypyridyl based sensitizer dyes with geminal dicarboxylic acid group as the binding unit for superior grafting of the dye to TiO₂ have been designed and synthesized. Steady-state photochemical studies of the two sensitizer dyes in presence of TiO₂ in water confirm strong binding of the dyes to TiO₂. Femtosecond transient absorption studies of these newly synthesized dyes on TiO₂ nanosurface have been carried out in water and the results have been compared with those for the corresponding 4,4′-dicarboxy-2,2′-bipyridine analogues of the dyes. While the charge recombination rates are considerably slower, interestingly, the electron injection rates are very fast for multiple saturated C–C linkages present between the chromophoric core and the anchoring moiety. The origin and the consequences of such profound effects on the ultrafast interfacial dynamics are discussed. This is the first report on the ultrafast transient absorption studies of dyes with geminal dicarboxylic acid binding groups, which we believe will add significantly to the present research efforts toward the development of robust and efficient dyes for use in dye solar applications