Hepatoma Metastasis-Inhibiting Supramolecular Nanoglycocalyx for Enhanced Type I Photodynamic Therapy.

Type I photodynamic therapy (PDT) is well demonstrated to have low oxygen dependency. However, fully suppressing the risk of hypoxia-induced tumor metastasis during PDT remains a great challenge. In this study, a tetra-lactosylated amphiphilic Aza-BODIPY glycocluster (TLBP) is reported that self-assembles into a supramolecular nanoglycocalyx on hepatoma cell membranes, serving as an artificial extracellular matrix (ECM) to inhibit hepatoma metastasis while facilitating efficient Type I PDT.

Preferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.

Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.

Protonation Weakens the Influence of Ribose on Triplet Decay of 2-Thiocytidine.

Long-lived triplet states are critical intermediates of thiobases for their applications in photodynamic therapy and as photoprobes for DNA/RNA-protein interactions, where thiobases are embedded in DNA/RNA and exist as thionucleosides. However, sugar moieties accelerate triplet decay rates, which is a common issue that must be resolved for thionucleosides. Here, we explore whether protonation of 2-thiocytosine (2tCyt) and 2-thiocytidine (2tCyd) under acidic pH can alter their triplet decays.

Multiphoton tandem photoredox catalysis of [Ir(dFCFppy)(dtbbpy)] facilitating radical acylation reactions.

Photoredox catalytic radical acylation reactions, utilizing [Ir(dFCFppy)(dtbbpy)] (IrIII) as the photocatalyst and α-keto acids as the starting substrates, have recently emerged as an attractive strategy for preparing ketone derivatives. While there is consensus on the importance of detailed mechanistic insights to maximize the formation of desired products, efforts focused on uncovering the underlying elementary mechanisms of IrIII photocatalytic radical acylation reactions are still lacking. Herein, using time-resolved spectroscopy, we observed the efficient quenching of the triplet state, IrIII*, electron transfer from α-keto acids, resulting in the generatation of the reduced IrII.

Alteration of the Expression and Functional Activities of Myosin II Isoforms in Enlarged Hyperplastic Prostates.

Introduction: Benign prostatic hyperplasia (BPH) is a common pathologic process in aging men, and the contraction of the prostatic smooth muscles (SMs) in the stroma plays a vital role in this pathogenesis, leading to lower urinary tract symptoms (LUTSs). The isoforms of both the SM myosin (SMM) and non-muscle myosin (NMM) are associated with the contraction type of the prostatic SMs, but the mechanism has not been fully elucidated.

Methods: We collected prostate tissues from 30 BPH patients receiving surgical treatments, and normal human prostate samples were obtained from 12 brain-dead men.

Dual Functionality of 6-Methylthioguanine: Synergistic Effects Enhancing the Photolability of DNA Nucleobases.

A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising applications in photochemotherapy treatment of cancers or pathogens. However, single substitution confers only limited phototoxicity to DNA. Herein, we combine femtosecond and nanosecond time-resolved spectroscopy with high-level calculations to disentangle the excited-state dynamics of 6-methylthioguanine (me6-TG) under variable wavelength UVA excitation (310-330 nm).

Complexed Photosensitizer of Hypericin with G-Quadruplex: Structure-Dependent Behavior.

Despite the increased interest of visible-light-absorbing compound Hypericin (Hyp) in photodiagnosis, photocatalysis, and photodynamic therapy (PDT) applications, a major obstacle still exists; i.e., the photoactivity is diminished due to the facile aggregation of Hyp in aqueous environment that induces excited-state quenching.

Fluorescence Quenching Dynamics of 2-Amino-7-methyl-1,8-naphthyridine in Abasic-Site-Containing DNA Duplexes for Nucleobase Recognition.

Dramatic fluorescence quenching of small heterocyclic ligands trapped in the abasic site (AP) of DNA has been implemented as an unprecedented strategy recognizing single-base mutations in sequence analysis of cancer genes. However, the key mechanisms governing selective nucleobase recognition remain to be disentangled. Herein, we perform fluorescence quenching dynamics studies for 2-amino-7-methyl-1,8-naphthyridine (AMND) in well-designed AP-containing DNA single/double strands.

Isovitexin alleviates hepatic fibrosis by regulating miR-21-mediated PI3K/Akt signaling and glutathione metabolic pathway: based on transcriptomics and metabolomics.

Background: Effective drugs for the treatment of hepatic fibrosis have not yet been identified. Isovitexin (IVT) is a promising hepatoprotective agent owing to its efficacy against acute liver injury. However, the role of IVT in liver fibrosis has not been reported.

Can methylated purine bases act as photoionization hotspots?

The direct photoionization of DNA canonical bases under ultraviolet radiation is difficult due to the high ionization potentials. According to previous quantum chemical calculations, methylation can have great influence on the ionization potential. Are methylated nucleobases prone to photoionization and cause DNA damage? As an important epigenetic modification in transcription, expression, and regulation of genes, it is of great biological significance to explore the effect of methylation on base photoionization from the experimental perspective.

H-NMR-based metabolomics study on the effects of raw and processed radix Wikstroemia indica on endogenous metabolites in rat plasma.

Based on metabolomics, to study the mechanism of Radix Wikstroemia indica (RWI) "Sweat soaking method" processing detoxification. The raw drug group and processed products was given raw RWI and processed RWI respectively by gavage. The control group was given the same amount of 1% sodium carboxy methyl cellulose distilled water by gavage.

Asiatic acid ameliorates rifampicin- and isoniazid-induced liver injury in vivo by regulating sphingolipid metabolism and mitogen-activated protein kinase signalling pathways.

In this study, we aimed to determine whether asiatic acid (AA) exerts any therapeutic effects on rifampicin (RFP)- and isoniazid (INH)-induced liver injury and elucidate the underlying mechanisms. Briefly, liver injury in mice was induced via RFP and INH administration. We investigated the effects and potential action mechanisms of AA on liver injury using transcriptomics, metabolomics and various examinations.

Sequence-specific binding behavior of coralyne toward triplex DNA: An ultrafast time-resolved fluorescence spectroscopy study.

Triplex DNA structure has potential therapeutic application in inhibiting the expression of genes involved in cancer and other diseases. As a DNA-targeting antitumor and antibiotic drug, coralyne shows a remarkable binding propensity to triplex over canonical duplex and thus can modulate the stability of triplex structure, providing a prospective gene targeting strategy. Much less is known, however, about coralyne-binding interactions with triplex.

TiO as a Nanozyme Mimicking Photolyase to Repair DNA Damage.

Cyclobutane pyrimidine dimer (CPD) is the most abundant DNA photolesion, and it can be repaired by photolyases based on electron-transfer mechanisms. However, photolyase is absent in the human body and lacks stability for applications. Can one develop natural enzyme mimetics utilizing nanoparticles (termed nanozymes) to mimic photolyase in repairing DNA damage? Herein, we observe the successful reversal of thymine dimer T<>T to normal T base by TiO under UVA irradiation.

Low Energy Photoionization of Phosphorothioate DNA-Oligomers and Ensuing Hole Transfer.

Phosphorothioate (PS) modified oligonucleotides (S-DNA) naturally exist in bacteria and archaea genome and are widely used as an antisense strategy in gene therapy. However, the introduction of PS as a redox active site may trigger distinct UV photoreactions. Herein, by time-resolved spectroscopy, we observe that 266 nm excitation of S-DNA d(A) and d(AA) leads to direct photoionization on the PS moiety to form hemi-bonded -P-S∴S-P- radicals, in addition to A base ionization to produce A/A(-H).

A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.

Daphnoretin (DAP), isolated from a traditional Chinese medicine (Linn. C. A.

Reminiscence therapy-based care program serves as an optional nursing modality in alleviating anxiety and depression, improving quality of life in surgical prostate cancer patients.

Purpose: Reminiscence therapy is reported to attenuate the psychological disorders in cancer patients, such as colorectal and lung cancer patients. However, relevant report on surgical prostate cancer patients is scarce. This study put forward a reminiscence therapy-based care program (RTCP + UC) combing reminiscence therapy with usual care (UC), and aimed to evaluate the impact of RTCP + UC on anxiety, depression, quality of life and survival in surgical prostate cancer patients.

Association of a Novel DOCK2 Mutation-Related Gene Signature With Immune in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality worldwide. Many studies have shown that dedicator of cytokinesis 2 (DOCK2) has a crucial role as a prognostic factor in various cancers. However, the potentiality of DOCK2 in the diagnosis of HCC has not been fully elucidated.

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats.

The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from Potentilla chinensis against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid significantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL.

Isovitexin protects against acute liver injury by targeting PTEN, PI3K and BiP via modification of m6A.

Isovitexin (IVT) has been shown to have a potential therapeutic effect on acute liver injury (ALI), but its underlying mechanisms especially the targets remain unclear, which was investigated in the present study. Briefly, the targets of IVT were predicted by bioinformatics and then were verified by multiple examinations using molecular docking, cellular thermal shift assay (CETSA), and Lipopolysaccharide/D-Galactosamine (LPS/D-GalN)-induced ALI animal model. The bioinformatic analysis predicted that the target genes of IVT against ALI were enriched into the PI3K/Akt and ERS-related pathways, in which, molecular docking and CETSA examination verified that the binding sites of IVT likely were PTEN, PI3K and BiP.

Free-Radical-Mediated Photoinduced Electron Transfer between 6-Thioguanine and Tryptophan Leading to DNA-Protein-Like Cross-Link.

The nucleobase analog 6-thioguanine (6-TG) has emerged as important immunosuppressant, anti-inflammatory, and anticancer drug in the past few decades, but its unique photosensitivity of absorbing strongly ultraviolet UVA light elicits photochemical hazards in many ways. The particularly intriguing yet unresolved question is whether the direct photoreaction of 6-TG can promote DNA-protein cross-links (DPCs) formation, which are large DNA adducts blocking DNA replication and physically impede DNA-related processes. Herein, by real-time observation of radical intermediates using time-resolved UV-vis absorption spectroscopy in conjunction with product analysis by HPLC-MS, we discover that UVA excitation of 6-TG triggers direct covalent cross-linking with tryptophan (TrpH) via an exquisite radical mechanism of electron transfer.

Reactivity and DNA Damage by Independently Generated 2'-Deoxycytidin-4-yl Radical.

Oxidative stress produces a variety of radicals in DNA, including pyrimidine nucleobase radicals. The nitrogen-centered DNA radical 2'-deoxycytidin-4-yl radical (dC·) plays a role in DNA damage mediated by one electron oxidants, such as HOCl and ionizing radiation. However, the reactivity of dC· is not well understood.

Rational design of an "all-in-one" phototheranostic.

We report here porphodilactol derivatives and their corresponding metal complexes. These systems show promise as "all-in-one" phototheranostics and are predicated on a design strategy that involves controlling the relationship between intersystem crossing (ISC) and photothermal conversion efficiency following photoexcitation. The requisite balance was achieved by tuning the aromaticity of these porphyrinoid derivatives and forming complexes with one of two lanthanide cations, namely Gd and Lu.

Ultrafast excited state dynamics and light-switching of [Ru(phen)(dppz)] in G-quadruplex DNA.

The triplet metal to ligand charge transfer (MLCT) luminescence of ruthenium (II) polypyridyl complexes offers attractive imaging properties, specifically towards the development of sensitive and structure-specific DNA probes. However, rapidly-deactivating dark state formation may compete with MLCT luminescence depending on different DNA structures. In this work, by combining femtosecond and nanosecond pump-probe spectroscopy, the MLCT relaxation dynamics of [Ru(phen)(dppz)] (phen = 1,10-phenanthroline, dppz = dipyridophenazine) in two iconic G-quadruplexes has been scrutinized.