Rosmarinic Acid, Active Component of Dansam-Eum Attenuates Ototoxicity of Cochlear Hair Cells through Blockage of Caspase-1 Activity

Cisplatin causes auditory impairment due to the apoptosis of auditory hair cells. There is no strategy to regulate ototoxicity by cisplatin thus far. Dansam-Eum (DSE) has been used for treating the central nerve system injury including hearing loss in Korea. However, disease-related scientific investigation by DSE has not been elucidated. Here, we demonstrated that DSE and its component rosmarinic acid (RA) were shown to inhibit apoptosis of the primary organ of Corti explants as well as the auditory cells. Administration of DSE and RA reduced the thresholds of the auditory brainstem response in cisplatin-injected mice. A molecular docking simulation and a kinetic assay show that RA controls the activity of caspase-1 by interaction with the active site of caspase-1. Pretreatment of RA inhibited caspase-1 downstream signal pathway, such as the activation of caspase-3 and 9, release of cytochrome c, translocation of apoptosis-inducing factor, up-regulation of Bax, down-regulation of Bcl-2, generation of reactive oxygen species, and activation of nuclear factor-κB. Anticancer activity by cisplatin was not affected by treatment with RA in SNU668, A549, HCT116, and HeLa cells but not B16F10 cells. These findings show that blocking a critical step by RA in apoptosis may be useful strategy to prevent harmful side effects of ototoxicity in patients with having to undergo chemotherapy

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Observations and models of low-mode internal waves in the ocean

The generation of internal gravity waves in the ocean is largely driven by tides, winds, and interaction of currents with the seafloor. Models and observations indicate a global energy supply for the internal wave field of about 1 TW by the conversion of barotropic tides at mid-ocean ridges and abrupt topographic features. Winds acting on the oceanic mixed layer contribute 0.3--1.5 TW, and mesoscale flow over rough topography adds about 0.2 TW. Globally, 1--2 TW are needed to maintain the observed stratification of the deep ocean by diapycnal mixing that results from the breaking of internal waves. Ocean circulation models show significant impact of the spatial distribution of internal wave dissipation and mixing on the ocean state, e.g., thermal structure, stratification, and meridional overturning circulation. Observations indicate that the local ratio of generation and dissipation of internal waves is often below unity, and thus, the energy available for mixing must be redistributed by internal tides and near-inertial waves at low vertical wavenumber that can propagate thousands of kilometers from their source regions. Eddy-permitting global ocean circulation models are able to quantify the different sources of energy input and can also simulate the propagation of the lowest internal wave modes. However, the variation of the internal wave energy flux along its paths by wave--wave interaction, topographic scattering, and refraction by mesoscale features as well as its ultimate fate by dissipation remains to be parameterized

An Imperative to Monitor Earth\u27s Energy Imbalance

The current Earth\u27s energy imbalance (EEI) is mostly caused by human activity, and is driving global warming. The absolute value of EEI represents the most fundamental metric defining the status of global climate change, and will be more useful than using global surface temperature. EEI can best be estimated from changes in ocean heat content, complemented by radiation measurements from space. Sustained observations from the Argo array of autonomous profiling floats and further development of the ocean observing system to sample the deep ocean, marginal seas and sea ice regions are crucial to refining future estimates of EEI. Combining multiple measurements in an optimal way holds considerable promise for estimating EEI and thus assessing the status of global climate change, improving climate syntheses and models, and testing the effectiveness of mitigation actions. Progress can be achieved with a concerted international effort