Synthesis and Anti-Neuroinflammatory Activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-Stimulated BV2 Microglia Via Inhibiting NF-κB/MAPK Signaling Pathways

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH₃O-, CH₃-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds CU-19 and CU-21 reduced the level of NO, TNF-α, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin.     

Activation of Stimulation of Interferon Genes (STING) Signal and Cancer Immunotherapy

Stimulator of interferon gene (STING), an intracellular receptor in the endoplasmic reticulum, could induce the production of cytokines such as type I interferon (IFN) by activating the cGAS-STING signal pathway. In recent years, activation of STING has shown great potential to enhance anti-tumor immunity and reshape the tumor microenvironment, which is expected to be used in tumor immunotherapy. A number of STING agonists have demonstrated promising biological activity and showed excellent synergistic anti-tumor effects in combination with other cancer therapies in preclinical studies and some clinical trials. The combination of STING agonists and ICI also showed a potent effect in improving anti-tumor immunity. In this review, we introduce the cGAS-STING signaling pathway and its effect in tumor immunity and discuss the recent strategies of activation of the STING signaling pathway and its research progress in tumor immunotherapy.     

Synthesis of Cobalt Bis(Dicarbollide)—Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).     

Electrochemical Immunoassay for Tumor Marker CA19-9 Detection Based on Self-Assembled Monolayer

A CA19-9 electrochemical immunosensor was constructed using a hybrid self-assembled membrane modified with a gold electrode and applied to detect real samples. Hybrid self-assembled membranes were selected for electrode modification and used to detect antigens. First, the pretreated working electrodes were placed in a 3-mercaptopropionic acid (MPA)/β-mercaptoethanol (ME) mixture for 24 h for self-assembly. The electrodes were then placed in an EDC/NHS mixture for 1 h. Layer modification was performed by stepwise dropwise addition of CA19-9 antibody, BSA, and antigen. Differential pulse voltammetry was used to characterize this immunosensor preparation process. The assembled electrochemical immunosensor enables linear detection in the concentration range of 0.05–500 U/mL of CA19-9, and the detection limit was calculated as 0.01 U/mL. The results of the specificity measurement test showed that the signal change of the interfering substance was much lower than the response value of the detected antigen, indicating that the sensor has good specificity and strong anti-interference ability. The repeatability test results showed that the relative standard deviations were less than 5%, showing good accuracy and precision. The CA19-9 electrochemical immunosensor was used for the actual sample detection, and the experimental results of the standard serum addition method showed that the RSD values of the test concentrations were all less than 10%. The recoveries were 102.4–115.0%, indicating that the assay has high precision, good accuracy, and high potential application value.     

Antioxidant Activity of Ruthenium Cyclopentadienyl Complexes Bearing Succinimidato and Phthalimidato Ligands

In these studies, we investigated the antioxidant activity of three ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η⁵-cyclopentadienyl)Ru(CO)₂-N-methoxysuccinimidato (1), (η⁵-cyclopentadienyl)Ru(CO)₂-N-ethoxysuccinimidato (2), and (η⁵-cyclopentadienyl)Ru(CO)₂-N-phthalimidato (3). We studied the effects of ruthenium complexes 1–3 at a low concentration of 50 µM on the viability and the cell cycle of peripheral blood mononuclear cells (PBMCs) and HL-60 leukemic cells exposed to oxidative stress induced by hydrogen peroxide (H₂O₂). Moreover, we examined the influence of these complexes on DNA oxidative damage, the level of reactive oxygen species (ROS), and superoxide dismutase (SOD) activity. We have observed that ruthenium complexes 1–3 increase the viability of both normal and cancer cells decreased by H₂O₂ and also alter the HL-60 cell cycle arrested by H₂O₂ in the sub-G1 phase. In addition, we have shown that ruthenium complexes reduce the levels of ROS and oxidative DNA damage in both cell types. They also restore SOD activity reduced by H₂O₂. Our results indicate that ruthenium complexes 1–3 bearing succinimidato and phthalimidato ligands have antioxidant activity without cytotoxic effect at low concentrations. For this reason, the ruthenium complexes studied by us should be considered interesting molecules with clinical potential that require further detailed research.     

Increase in the Intracellular Bulk Water Content in the Early Phase of Cell Death of Keratinocytes,Corneoptosis, as Revealed by 65 GHz Near-Field CMOS Dielectric Sensor

While bulk water and hydration water coexist in cells to support the expression of biological macromolecules, how the dynamics of water molecules, which have long been only a minor role in molecular biology research, relate to changes in cellular states such as cell death has hardly been explored so far due to the lack of evaluation techniques. In this study, we developed a high-precision measurement system that can discriminate bulk water content changes of ±0.02% (0.2 mg/cm³) with single-cell-level spatial resolution based on a near-field CMOS dielectric sensor operating at 65 GHz. We applied this system to evaluate the temporal changes in the bulk water content during the cell death process of keratinocytes, called corneoptosis, using isolated SG1 (first layer of stratum granulosum) cells in vitro. A significant irreversible increase in the bulk water content was observed approximately 1 h before membrane disruption during corneoptosis, which starts with cytoplasmic high Ca²⁺ signal. These findings suggest that the calcium flux may have a role in triggering the increase in the bulk water content in SG1 cells. Thus, our near-field CMOS dielectric sensor provides a valuable tool to dissect the involvement of water molecules in the various events that occur in the cell.     

Wafer thickness optimization for silicon solar cells of heterogeneous material quality

In this Letter, we introduce a method of calculating the optimal wafer thickness for silicon solar cells with multicrystalline bulk material. The optimal thickness depends on the relation of bulk recombination to surface recombination and the light trapping. For multicrystalline silicon bulk recombination strongly varies laterally and with injection level, which complicates the calculations. A thickness optimization using the “Efficiency Limiting Bulk Recombination Analysis” (ELBA) takes all these effects correctly into account. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Role of Intracellular Iron in Switching Apoptosis to Ferroptosis to Target Therapy-Resistant Cancer Stem Cells

Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.     

Raman spectroscopic study on classification of cervical cell specimens

Cervix-cancer is the third most common female cancer worldwide. Papanicolaou (Pap) test, a well-recognized screening tool, is labor intensive, time consuming and prone to subjective interpretations. Optical spectroscopic methods, sensitive to molecular changes are being pursued as potential diagnostics tool. In this study we have explored Raman spectroscopic approach to differentiate exfoliated cell pellets using 94 cervical cell specimens (45-normal and 49-abnormal specimens). Study was carried out by two approaches. In the first approach, spectral data from 37 cell specimens were acquired and analyzed by Principal Component-Linear Discriminant Analysis (PC-LDA), which yielded classification efficiencies of 86% and 84% for normal and abnormal specimens, respectively. Mean and difference spectra suggest presence of blood in abnormal specimen as a major cause of discrimination. However, as tumor is vascular, bleeding was observed during abnormal sample collection. Hence, spectra of abnormal specimens show heme and fibrin features, and this can lead to false interpretations, as bleeding also occur in several non-cancerous conditions. Therefore, remaining 57 specimens were treated with Red Blood Corpuscles (RBC) lysis buffer in order to remove the RBC influence. PC-LDA resulted classification efficiency of about 79% and 78% for normal and abnormal smear, respectively – comparable to Pap test. Thus finding of the study suggests feasibility of Raman spectroscopic classification of normal and cancerous exfoliated cervical cell specimens.