Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy

Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors’ quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol’s therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol’s anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients

Timing and characteristics of nuclear events during conjugation and genomic exclusion in Paramecium multimicronucleatum

Ciliated protists are ideal material for studying the origin and evolution of sex, because of their nuclear dimorphism (containing both germline micronucleus and somatic macronucleus in the same cytoplasm), special sexual processes (conjugation and autogamy), and high diversity of mating-type systems. However, the study of sexual process is limited to only a few species, due to the difficulties in inducing or observing conjugation. In the present study, we investigate the conjugation process in Paramecium multimicronucleatum: (1) of the three prezygotic divisions, all micronuclei undergo the first two divisions (meiosis I, II), while a variable number of nuclei undergo the third division (mitosis); (2) the synkaryon divides three times after fertilization, giving rise to eight products that differentiate into four macronuclear anlagen and four micronuclei; (3) cells restore the vegetative stage after two successive cell fissions during which the macronuclear anlagen are distributed into daughter cells without division, while micronuclei divide mitotically; (4) the parental macronucleus begins to fragment following the first meiotic division and finally degenerates completely; (5) the entire process takes about 110 h, of which about 85 h are required for macronuclear development. In addition, we describe for the first time the process of genomic exclusion occurring between amicronucleate and micronucleate cells of P. multimicronucleatum, during which the micronucleate cell contributes a pronucleus to the amicronucleate cell, resulting in both exconjugants being homozygotes. These results provide new insights into the diversity of sexual processes and lay an important cytological basis for future in-depth studies of mating systems in ciliates

Enhanced functional properties of CeO2 modified graphene/epoxy nanocomposite coating through interface engineering

This paper reports significant enhancement of corrosion resistance and electrical properties of waterborne epoxy coatings through additions of ceria modified graphene. Results showed that ceria particles were uniformly distributed and covalently bonded onto the surface of graphene. A dense interface layer was formed between the ceria modified graphene and epoxy matrix by aliphatic ether bonds. The composite coating with a modified graphene content of 0.5 wt% exhibited the best corrosion resistance with the highest impedance modulus (e.g., 103 Ω cm2 for the damaged coating) and the lowest corrosion rate (e.g., 0.002 mm/year). The excellent corrosion resistance of the composite coating is related to the barrier effect of graphene and the inhibition effect of ceria on metal corrosion. Moreover, the coating showed a low percolation threshold of 0.231 vol% and its electrical conductivity reached 10−5 S/m when the content of modified graphene was 0.5 wt%

Lipid-lowering drugs affect lung cancer risk via sphingolipid metabolism: a drug-target Mendelian randomization study

Background: The causal relationship between lipid-lowering drug (LLD) use and lung cancer risk is controversial, and the role of sphingolipid metabolism in this effect remains unclear.Methods: Genome-wide association study data on low-density lipoprotein (LDL), apolipoprotein B (ApoB), and triglycerides (TG) were used to develop genetic instrumental variables (IVs) for LLDs. Two-step Mendelian randomization analyses were performed to examine the causal relationship between LLDs and lung cancer risk. The effects of ceramide, sphingosine-1-phosphate (S1P), and ceramidases on lung cancer risk were explored, and the proportions of the effects of LLDs on lung cancer risk mediated by sphingolipid metabolism were calculated.Results:APOB inhibition decreased the lung cancer risk in ever-smokers via ApoB (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.70–0.92, p = 0.010), LDL (OR 0.82, 95% CI 0.71–0.96, p = 0.040), and TG (OR 0.63, 95% CI 0.46–0.83, p = 0.015) reduction by 1 standard deviation (SD), decreased small-cell lung cancer (SCLC) risk via LDL reduction by 1 SD (OR 0.71, 95% CI 0.56–0.90, p = 0.016), and decreased the plasma ceramide level and increased the neutral ceramidase level. APOC3 inhibition decreased the lung adenocarcinoma (LUAD) risk (OR 0.60, 95% CI 0.43–0.84, p = 0.039) but increased SCLC risk (OR 2.18, 95% CI 1.17–4.09, p = 0.029) via ApoB reduction by 1 SD. HMGCR inhibition increased SCLC risk via ApoB reduction by 1 SD (OR 3.04, 95% CI 1.38–6.70, p = 0.014). The LPL agonist decreased SCLC risk via ApoB (OR 0.20, 95% CI 0.07–0.58, p = 0.012) and TG reduction (OR 0.58, 95% CI 0.43–0.77, p = 0.003) while increased the plasma S1P level. PCSK9 inhibition decreased the ceramide level. Neutral ceramidase mediated 8.1% and 9.5% of the reduced lung cancer risk in ever-smokers via ApoB and TG reduction by APOB inhibition, respectively, and mediated 8.7% of the reduced LUAD risk via ApoB reduction by APOC3 inhibition.Conclusion: We elucidated the intricate interplay between LLDs, sphingolipid metabolites, and lung cancer risk. Associations of APOB, APOC3, and HMGCR inhibition and LPL agonist with distinct lung cancer risks underscore the multifaceted nature of these relationships. The observed mediation effects highlight the considerable influence of neutral ceramidase on the lung cancer risk reduction achieved by APOB and APOC3 inhibition

Conformation-Dependent Exonuclease III Activity Mediated by Metal Ions Reshuffling on Thymine-Rich DNA Duplexes for an Ultrasensitive Electrochemical Method for Hg2+ Detection

Hg2+ is known to bind very strongly with TT mismatches in DNA duplexes to form THg2+T base pairs, the structure of which is stabilized by covalent NHg bonds and exhibits bonding strength higher than hydrogen bonds. In this work, we exploit exonuclease III (Exo III) activity on DNA hybrids containing THg2+T base pairs and our experiments show that Hg2+ ions could intentionally trigger the activity of Exo III toward a designed thymine-rich DNA oligonucleotide (e-T-rich probe) by the conformational change of the probe. Our sensing strategy utilizes this conformation-dependent activity of Exo III, which is controlled through the cyclical shuffling of Hg2+ ions between the solution phase and the solid DNA hybrid. This interesting attribute has led to the development of an ultrasensitive detection platform for Hg2+ ions with a detection limit of 0.2 nM and a total assay time within minutes. This simple detection strategy could be used for the detection of other metal ions which exhibit specific interactions with natural or synthetic bases

Ultrasensitive Solution-Phase Electrochemical Molecular Beacon-Based DNA Detection with Signal Amplification by Exonuclease III-Assisted Target Recycling

Taking advantage of the preferential exodeoxyribonuclease activity of exonuclease III in combination with the difference in diffusivity between an oligonucleotide and a mononucleotide toward a negatively charged ITO electrode, a highly sensitive and selective electrochemical molecular beacon (eMB)-based DNA sensor has been developed. This sensor realizes electrochemical detection of DNA in a homogeneous solution, with sensing signals amplified by an exonuclease III-based target recycling strategy. A hairpin-shaped oligonucleotide containing the target DNA recognition sequence, with a methylene blue tag close to the 3' terminus, is designed as the signaling probe. Hybridization with the target DNA transforms the probe's exonuclease III-inactive protruding 3' terminus into an exonuclease III-active blunt end, triggering the digestion of the probe into mononucleotides including a methylene blue-labeled electroactive mononucleotide (eNT). The released eNT, due to its less negative charge and small size, diffuses easily to the negative ITO electrode, resulting in an increased electrochemical signal. Meanwhile, the intact target DNA returns freely to the solution and hybridizes with other probes, releasing multiple eNTs and thereby further amplifies the electrochemical signal. This new immobilization-free, signal-amplified electrochemical DNA detection strategy shows great potential to be integrated in portable and cost-effective DNA sensing devices

A new solution-phase electrochemical DNA detection platform with target recycling-based signal amplification

We report a rapid, ultrasensitive, immobilization-free and signal-on electrochemical DNA biosensor with excellent discrimination ability for single-nucleotide polymorphisms. It achieves recognition signal generation by the specific cleavage function of exonuclease III and the diffusion different between oligonucleotides and mononucleotides towards a negatively charged ITO electrode surface. Meanwhile, signal can be further amplified by target recycling resulting from the probe digestion process. Combining the advantages of immobilization-free electrochemical detection and isothermal signal amplification strategy, the presented approach may represent a promising path toward direct DNA detection at the point of care

Organic Electrochemical Transistors Integrated in Flexible Microfluidic Systems and Used for Label-Free DNA Sensing

Organic electrochemical transistors are integrated in flexible microfluidic systems. A novel label-free DNA sensor is developed based on devices with single-stranded DNA probes immobilized on gate electrodes. These devices successfully detect complementary DNA targets at low concentrations using a pulse-enhanced hybridization technique in microfluidic channels. Organic electrochemical transistors are excellent candidates for flexible, highly sensitive, and low-cost biosensors

Gate-voltage control of angular and spatial shifts for a dielectric slab containing graphene

By theoretically considering a dielectric slab containing graphene, we investigate the effect of the graphene layer on the angular Goos-Hänchen (AGH) shifts and the transverse angular and spatial shifts from the spin-Hall effect of light (SHEL) for the reflection of a light beam. Through manipulating the voltage applied to graphene via an exterior gate, it was found that near the transmission resonance of the slab containing graphene, the giant and tunable AGH shifts and transverse shifts (TS) for both s-polarized and p-polarized waves are present. We also find that near the normal incident angle, the giant and tunable TS from SHEL for both s-polarized and p-polarized waves can occur on the interface containing graphene. It is expected that these phenomena can result in significant interesting and novel applications of graphene in all kinds of optical devices, and more