The Affinity of Carboplatin to B-Vitamins and Nucleobases

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

Soluble Pecam-1 as a Biomarker in Periprosthetic Joint Infection

A reliable workup with regard to a single diagnostic marker indicating periprosthetic joint infection (PJI) with sufficient sensitivity and specificity is still missing. The immunologically reactive molecule Pecam-1 is shed from the T-cell surface upon activation via proinflammatory signaling, e.g., triggered by specific pathogens. We hypothesized that soluble Pecam-1 (sPecam-1) can hence function as a biomarker of PJI. Fifty-eight patients were prospectively enrolled and assigned to one of the respective treatment groups (native knees prior to surgery, aseptic, and septic total knee arthroplasty (TKA) revision surgeries). Via synovial sample acquisition and ELISA testing, a database on local sPecam-1 levels was established. We observed a significantly larger quantity of sPecam-1 in septic (n = 22) compared to aseptic TKA revision surgeries (n = 20, p ≤ 0.001). Furthermore, a significantly larger amount of sPecam-1 was found in septic and aseptic revisions compared to native joints (n = 16, p ≤ 0.001). Benchmarking it to the gold standard showed a high predictive power for the detection of PJI. Local sPecam-1 levels correlated to the infection status of the implant, and thus bear a strong potential to act as a biomarker of PJI. While a clear role of sPecam-1 in infection could be demonstrated, the underlying mechanism of the molecule’s natural function needs to be further unraveled.

Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction

Formaldehyde (FA) has long been considered as a toxin and carcinogen due to its damaging effects to biological macromolecules, but its beneficial roles have been increasingly appreciated lately. Real-time monitoring of this reactive molecule in living systems is highly desired in order to decipher its physiological and/or pathological functions, but a genetically encoded FA sensor is currently lacking. We herein adopt a structure-based study of the underlying mechanism of the FA-responsive transcription factor HxlR from Bacillus subtilis, which shows that HxlR recognizes FA through an intra-helical cysteine-lysine crosslinking reaction at its N-terminal helix α1, leading to conformational change and transcriptional activation. By leveraging this FA-induced intra-helical crosslinking and gain-of-function reorganization, we develop the genetically encoded, reaction-based FA sensor—FAsor, allowing spatial-temporal visualization of FA in mammalian cells and mouse brain tissues.

Zinc Complex Based Multifunctional Reactive Lithium Polysulfide Trapper Approaching Its Theoretical Efficiency

The “shuttle effect” of soluble lithium polysulfides (LPS), which causes rapid capacity fading, remains a lingering issue for lithium-sulfur batteries (LSBs). Herein, we report a new type of reactive molecule-based (or molecular) LPS trapper, zinc acetate-diethanolamine (Zn(OAc)2·DEA), which demonstrated a molecular efficiency of 1.8 for LPS trapping, approaching its theoretical limit of 2. This is the highest trapping capability among all reported LPS trappers. During discharge the trapped polysulfides are much more thermodynamically favored for reduction compared to the non-trapped ones, while during charge the complex Zn(SLi)2·DEA formed in the previous discharging process can be more easily oxidized due to its lower energy barrier in comparison to Li2S, indicating the catalytic effects of Zn2+·DEA on the redox of sulfur species. Zn(OAc)2·DEA is also an excellent binder owing to its multiple intermolecular hydrogen bonds. LSBs using Zn(OAc)2·DEA as a LPS trapper, a binder, and a redox catalyst exhibited excellent long-term cycling stability (with a capacity retention of 85% after 1000 cycles at a rate of 0.5 C) and enhanced rate performance. The work demonstrated the potential of this novel type of multifunctional metal complex-based reactive molecular LPS trappers for high capacity and stable LSBs.

TMPE Derived from Saffron Natural Monoterpene as Cytotoxic and Multidrug Resistance Reversing Agent in Colon Cancer Cells

Terpenes constitute one of the largest groups of natural products. They exhibit a wide range of biological activities including antioxidant, anticancer, and drug resistance modulating properties. Saffron extract and its terpene constituents have been demonstrated to be cytotoxic against various types of cancer cells, including breast, liver, lung, pancreatic, and colorectal cancer. In the present work, we have studied anticancer properties of TMPE, a newly synthesized monoterpene derivative of β-cyclocitral—the main volatile produced by the stigmas of unripe crocuses. TMPE presented selective cytotoxic activity to doxorubicin-resistant colon cancer cells and was identified to be an effective MDR modulator in doxorubicin-resistant cancer cells. Synergy between this derivative and doxorubicin was observed. Most probably, TMPE inhibited transport activity of ABCB1 protein without affecting its expression level. Analysis of TMPE physicochemical parameters suggested it was not likely to be transported by ABCB1. Molecular modeling showed TMPE being more reactive molecule than the parental compound—β-cyclocitral. Analysis of electrostatic potential maps of both compounds prompted us to hypothesize that reduced reactivity as well as susceptibility to electrophilic attack were related to the lower general toxicity of β-cyclocitral. All of the above pointed to TMPE as an interesting candidate molecule for MDR reversal in cancer cells.

Resveratrol in Cancer Patients: From Bench to Bedside

Resveratrol (3,5,4′-trihydroxystilbene) is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.

Antioxidant Potential of Madura Knife Scallop (Solen sp) Extract as a Prevention of Oxidative Stress

Reactive Oxygen Species (ROS) are produced by humans as a result of cellular metabolism and environmental factors such as pollutants or cigarette smoke. ROS is a very reactive molecule and has the ability to damage cell structure. Oxidative stress is a condition between oxidants and antioxidants that is not balance, pathophysiologically, oxidative stress can trigger the risk of various diseases including hypertension, atherosclerosis, diabetes, heart failure, stroke and other chronic diseases. Oxidative stress can be overcome by intake of antioxidants. The purpose of this study was to determine the antioxidant activity contained in the meat and shells of a knife scallop (Solen sp.) that lives in Bangkalan waters, Madura. The method used in this study is an analysis of antioxidant activity with the DPPH method. Knife scallop has antioxidant activity which is evident from the IC50 values obtained. IC50 values of the shell and meat extract with ethanol solvent were 489.56 ppm and 748.49 ppm. IC50 values of the shell and meat extract with ethyl acetate solvent were 916.43 ppm and 2045.93 ppm. While the IC50 value of the shell and meat extract with chloroform solvent was 119.37 ppm and 1692.80 ppm. Based on IC50 data of knife scallop shell and meat extracts on the 3 types of solvents, it can be concluded that knife scallop’s shell and meat extract with ethanol solvent has the greatest antioxidant activity compared to ethyl acetate and chloroform solvents.

Double and Triple Ionisation of Isocyanic Acid

Double and triple ionisation spectra of the reactive molecule isocyanic acid (HNCO) have been measured using multi-electron and ion coincidence techniques combined with synchrotron radiation and compared with high-level theoretical calculations. Vertical double ionisation at an energy of 32.8 ± 0.3 eV forms the 3A” ground state in which the HNCO2+ ion is long lived. The vertical triple ionisation energy is determined as 65 ± 1 eV. The core-valence double ionisation spectra resemble the valence photoelectron spectrum in form, and their main features can be understood on the basis of a simple and rather widely applicable Coulomb model based on the characteristics of the molecular orbitals from which electrons are removed. Characteristics of the most important dissociation channels are examined and discussed.

Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens.

4-Hydroxy-Trans-2-Nonenal in the Regulation of Anti-Oxidative and Pro-Inflammatory Signaling Pathways

Recent studies indicate that 4-hydroxy-trans-2-nonenal (HNE), a major oxidative stress triggered lipid peroxidation-derived aldehyde, plays a critical role in the pathophysiology of various human pathologies including metabolic syndrome, diabetes, cardiovascular, neurological, immunological, and age-related diseases and various types of cancer. HNE is the most abundant and toxic α, β-unsaturated aldehyde formed during the peroxidation of polyunsaturated fatty acids in a series of free radical-mediated reactions. The presence of an aldehyde group at C1, a double bond between C2 and C3 and a hydroxyl group at C4 makes HNE a highly reactive molecule. These strong reactive electrophilic groups favor the formation of HNE adducts with cellular macromolecules such as proteins and nucleic acids leading to the regulation of various cell signaling pathways and processes involved in cell proliferation, differentiation, and apoptosis. Many studies suggest that the cell-specific intracellular concentrations of HNE dictate the anti-oxidative and pro-inflammatory activities of this important molecule. In this review, we focused on how HNE could alter multiple anti-oxidative defense pathways and pro-inflammatory cytotoxic pathways by interacting with various cell-signaling intermediates.