Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

Emerging disinfection byproducts 3-bromine carbazole induces cardiac developmental toxicity via aryl hydrocarbon receptor activation in zebrafish larvae.

3-bromine carbazole (3-BCZ) represents a group of emerging aromatic disinfection byproducts (DBP) detected in drinking water; however, limited information is available regarding its potential cardiotoxicity. To assess its impacts, zebrafish embryos were exposed to 0, 0.06, 0.14, 0.29, 0.58, 1.44 or 2.88 mg/L of 3-BCZ for 120 h post fertilization (hpf). Our results revealed that ≥1.44 mg/L 3-BCZ exposure induced a higher incidence of heart malformation and an elevated pericardial area in zebrafish larvae; it also decreased the number of cardiac muscle cells and thins the walls of the ventricle and atrium while increasing cardiac output and impeding cardiac looping. Furthermore, 3-BCZ exposure also exhibited significant effects on the transcriptional levels of genes related to both cardiac development (nkx2.5, vmhc, gata4, tbx5, tbx2b, bmp4, bmp10, and bmp2b) and cardiac function (cacna1ab, cacna1da, atp2a1l, atp1b2b, atp1a3b, and tnnc1a). Notably, N-acetyl-L-cysteine, a reactive oxygen species scavenger, may alleviate the failure of cardiac looping induced by 3-BCZ but not the associated cardiac dysfunction or malformation; conversely, the aryl hydrocarbon receptor agonist CH131229 can completely eliminate the cardiotoxicity caused by 3-BCZ. This study provides new evidence for potential risks associated with ingesting 3-BCZ as well as revealing underlying mechanisms responsible for its cardiotoxic effects on zebrafish embryos.

[Bionic optic nerve based on perovskite (CsPbBr 3) quantum-dots].

The bionic optic nerve can mimic human visual physiology and is a future treatment for visual disorders. Photosynaptic devices could respond to light stimuli and mimic normal optic nerve function. By modifying (Poly(3,4-ethylenedioxythio-phene):poly (styrenesulfonate)) active layers with all-inorganic perovskite quantum dots, with an aqueous solution as the dielectric layer in this paper, we developed a photosynaptic device based on an organic electrochemical transistor (OECT). The optical switching response time of OECT was 3.7 s. To improve the optical response of the device, a 365 nm, 300 mW·cm -2 UV light source was used. Basic synaptic behaviors such as postsynaptic currents (0.225 mA) at a light pulse duration of 4 s and double pulse facilitation at a light pulse duration of 1 s and pulse interval of 1 s were simulated. By changing the way light stimulates, for example, by adjusting the intensity of the light pulses from 180 to 540 mW·cm -2, the duration from 1 to 20 s, and the number of light pulses from 1 to 20, the postsynaptic currents were increased by 0.350 mA, 0.420 mA, and 0.466 mA, respectively. As such, we realized the effective shift from short-term synaptic plasticity (100 s recovery of initial value) to long-term synaptic plasticity (84.3% of 250 s decay maximum). This optical synapse has a high potential for simulating the human optic nerve.

Anti-Leukemia Activity of Polysaccharide from Sargassum fusiforme via the PI3K/AKT/BAD Pathway In Vivo and In Vitro.

Studies have shown that Sargassum fusiforme and its extracts are effective herbal treatments for leukemia. We previously found that a polysaccharide from Sargassum fusiforme, SFP 2205, stimulated apoptosis in human erythroleukemia (HEL) cells. However, the structural characterization and antitumoral mechanisms of SFP 2205 remain uncertain. Here, we studied the structural characteristics and anticancer mechanisms of SFP 2205 in HEL cells and a xenograft mouse model. The results demonstrated that SFP 2205, with a molecular weight of 41.85 kDa, consists of mannose, rhamnose, galactose, xylose, glucose, and fucose with monosaccharides composition of 14.2%, 9.4%, 11.8%, 13.7%, 11.0%, and 38.3%, respectively. On animal assays, SFP 2205 significantly inhibited growth of HEL tumor xenografts with no discernible toxicity to normal tissues. Western blotting showed that SFP 2205 therapy improved Bad, Caspase-9, and Caspase-3 protein expression, and ultimately induced HEL tumor apoptosis, indicating mitochondrial pathway involvement. Furthermore, SFP 2205 blocked the PI3K/AKT signaling pathway and 740 Y-P, an activator of the PI3K/AKT pathway, rescued the effects of SFP 2205 on HEL cell proliferation and apoptosis. Overall, SFP 2205 may be a potential functional food additive or adjuvant for preventing or treating leukemia.

Recent research progress in CDs@MOFs composites: fabrication, property modulation, and application.

Carbon dots (CDs) have exhibited a promising application prospect in many fields because of their good fluorescence properties, biocompatibility, low toxicity, and easy functionalization. In order to improve their photoelectricity and stability, metal-organic frameworks (MOFs) can be used as host materials to provide ideal carriers for CDs to realize the multifunctional composites of CDs and MOFs (CDs@MOFs). At present, CDs@MOFs composites have shown tremendous application potential because they have various advantages of both CDs and MOFs. In this review, the synthesis methods of CDs@MOFs composites are firstly introduced. Then, the influence of the synergy between CDs and MOFs on the regulation of their structures and optical properties is highlighted. Furthermore, the recent application researches of CDs@MOFs composites in fluorescent probes, solid-state lighting, and photoelectrocatalysis are generalized. Finally, the critical issues, challenges, and solutions on their structure and property regulation and application are put forward, and their commercialization direction is also prospected.

Aptamer-Functionalized Upconverting Nanoformulations for Light-Switching Cancer-Specific Recognition and In Situ Photodynamic-Chemo Sequential Theranostics.

Biomarker-activatable theranostic formulations offer the potential for removing specific tumors with a high diagnostic accuracy and a significant pharmacological effect. Herein, we developed a novel activatable theranostic nanoformulation UAS-PD [upconversion nanophosphor (UCNP)-aptamer/ssDNA-pyropheophorbide-a (PPA)-doxyrubicin (DOX)], which can recognize specific cancer cells with sensitivity and trigger the localized photodynamic destruction and enhanced chemotherapy. UAS-PD was constructed by the conjugation of UCNPs and aptamer probes containing the photosensitizer PPA and the chemotherapeutic drug DOX. When cancer cells are present, the UAS-PD specifically binds to PTK7, an overexpressed protein present on the surface of cancer cells, through conformational recombination of the aptamer structure and switches its upconversion luminescence from 655 to 540 nm. This long-lived ratiometric optical signal provides an ultrasensitive detection limit as low as 3.9 nM for PTK7. Changes in the conformation of UAS-PD can also induce PPA to approach UCNPs, which can produce cytotoxic singlet oxygens under near-infrared excitation to destroy the cell membrane and enhance its permeability for the simultaneously released DOX that targets cellular DNA degradation, which results in a highly effective tumor-killing effect by synergistic extra-intracellular sequential damage.

The natural phenolic peperobtusin A induces apoptosis of lymphoma U937 cells via the Caspase dependent and p38 MAPK signaling pathways.

Our previous research found the ethyl acetate extract of Peperomia tetraphylla (EAEPT) inhibited the growth of U937 cells by blocking the cell cycle and prompted apoptosis via the reactive oxygen species (ROS)-medicated mitochondria pathway. While the compounds in EAEPT which possessed the anti-tumor activity were unclear. Peperobtusin A is a phenolic compound, which was isolated from the whole plant of Peperomia tetraphylla. In this work, we found that peperobtusin A had the anti-proliferative effects against human lymphoma U937 cells and induced apoptosis in a dose dependent manner. Peperobtusin A significantly enhanced the formation of intracellular ROS and induced the loss of mitochondrial membrane potential (Δψm). And peperobtusin A could increase the ratio of Bax/Bcl-2, induce the cleavage of Bid, Caspase-3, Caspase-8 and Caspase-9 and enhance the level of P-P38. Moreover, peperobtusin A induced the accumulation of cells at S phase. Through using of inhibitors such as antioxidant NAC, pan-caspase inhibitor Z-VAD-FMK, p38 MAPK specific inhibitor SB203580, we found that intracellular ROS generation, activation of Caspases and p38 MAPK played very important roles in the apoptosis induced by peperobtusin A in U937 cells. Our results indicated that intracellular ROS generation, the Caspase-dependent and p38 MAPK signaling pathways involved in apoptosis induced by peperobtusin A in U937 cells.

RGD peptide-modified fluorescent gold nanoclusters as highly efficient tumor-targeted radiotherapy sensitizers.

Radiotherapy is a leading treatment approach of cancer therapy. While it is effective in killing tumor cells, it can also cause serious damage to surrounding normal tissue. Targeted radiotherapy with gold nanoparticle-based radiosensitizers is actively being investigated, and considered as a promising means to enhance the efficacy of radiotherapy against tumors under a relatively low and safe radiation dose. In this work, we report a green and one-step strategy to synthesize fluorescent gold nanoclusters by using a commercialized cyclic arginine-glycine-aspartic acid (c(RGDyC)) peptide as the template. The nanoclusters inherit special properties of both the Au core (red/NIR fluorescence emission and strong radiosensitizing effect) and c(RGDyC) shell (active cancer cell-targeting ability and good biocompatibility), and can be applied as fluorescent probes to stain αvß3 integrin-positive cancer cells, as well as radiosensitizing agents to boost the killing efficacy of radiotherapy. Our data suggest that the as-designed gold nanoclusters have excellent biocompatibility, bright red/NIR fluorescence, active tumor targeting property, and strong radiosensitizing effect, making them highly promising towards potential clinical translation.

Glutathione-capped, renal-clearable CuS nanodots for photoacoustic imaging and photothermal therapy.

The development of functional nanomaterials that undergo renal clearance is of fundamental importance to their in vivo biomedical applications. In this work, we report a one-pot method for the preparation of ultrasmall copper sulfide nanodots capped with a small natural tripeptide glutathione (GSH-CuS NDs). The GSH-CuS NDs had a hydrodynamic diameter of 5.8 nm, smaller than the reported polymer-coated CuS NDs with similar core sizes, and exhibited strong optical absorption and conversion at the near-infrared (NIR) region, leading to a sufficient photohyperthermic effect under the irradiation of a 980 nm laser. In vivo studies showed that the GSH-CuS NDs could induce significant photoacoustic imaging signal enhancement and remarkable photothermal therapy efficacy. Importantly, biodistribution studies and MRI imaging showed that the GSH-CuS NDs could freely circulate in the blood pool without undesirable accumulation in the liver and spleen, and could be naturally removed from the body through renal clearance, making them attractive for practical theranostic applications.

Electrochemical determination of estrogenic compound bisphenol F in food packaging using carboxyl functionalized multi-walled carbon nanotubes modified glassy carbon electrode.

A simple and highly sensitive electroanalytical method for the determination of bisphenol F (BPF) was developed, which was carried out on multi-walled carbon nanotubes-COOH (MWCNT-COOH) modified glassy carbon electrode (GCE) using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results showed that MWCNT-COOH remarkably enhanced the oxidation of BPF, which improved the anodic peak current of BPF significantly. The mechanism was oxidation of BPF lose electrons on the electrode surface via adsorption-controlled process, electrode reaction is the two electrons/two protons process. Under the optimised conditions, the oxidation peak current was proportional to BPF concentration the range from 0.12 to 6.01 µg mL(-1). The detection limit was 0.11 µg mL(-1) (S/N=3), and the relative standard deviation (R.S.D.) was 3.5% (n=9). Moreover, the MWCNT-COOH/GCE electrode showed good reproducibility, stability and anti-interference. Therefore, the proposed method was successfully applied to determine BPF in food packing and the results were satisfactory.

(E)-N-Benzyl-ideneadamantan-1-amine.

In the title compound, C(17)H(21)N, the dihedral angle between the benzene ring and the imine group (-N=) is 5.1 (4)°. In the adamantane group, the C-C-C bond angles range from 107.88 (19) to 111.33 (17)°. Only weak van der Waals inter-actions contribute to the contribute to the packing of the molecules in the crystal..

2-[(Adamantan-1-yl)amino-meth-yl]-4-chloro-phenol hemihydrate.

In the title compound, C17H22ClNO·0.5H2O, the water mol-ecule O atom resides on a twofold rotation axis. In the organic mol-ecule, the phenol group forms an intra-molecular O-H⋯N hydrogen bond. In the crystal, pairs of organic mol-ecules are hydrogen bonded through bridging solvent water mol-ecules, forming chains along the b-axis direction.

rac-2-{[1-(1-Adamant-yl)eth-yl]imino-meth-yl}-5-meth-oxy-phenol.

A novel Schiff base compound, C(20)H(27)NO(2), was obtained by a condensation of rimantadine and 2-hy-droxy-4-meth-oxy-benzaldehyde. An intra-molecular O-H⋯N hydrogen bond supports the phenol-imine tautomeric form. The adamantane and imino-methyl-4-meth-oxy-phenol units are arranged in a folded conformation [C-N-C-C torsion angle = 110.9 (3)°]. In the crystal, highly hydro-phobic adamantane moieties are inserted between the imino-methyl-4-meth-oxy-phenol units in a sandwich-like arrangement along the c axis.

Spectroscopic analyses on interaction of Amantadine-Salicylaldehyde, Amantadine-5-Chloro-Salicylaldehyde and Amantadine-o-Vanillin Schiff-Bases with bovine serum albumin (BSA).

In this work, three Tricyclo [3.3.1.1(3,7)] decane-1-amine (Amantadine) Schiff-Bases, Amantadine-Salicylaldehyde (AS), Amantadine-5-Chloro-Salicylaldehyde (AS-5-C) and Amantadine-o-Vanillin (AS-o-V), were synthesized by direct heating reflux method in ethanol solution and characterized by infrared spectrum and elementary analysis. Fluorescence quenching was used to study the interaction of these Amantadine Schiff-Bases (AS, AS-5-C and AS-o-V) with bovine serum albumin (BSA). According to fluorescence quenching calculations the bimolecular quenching constant (K(q)), apparent quenching constant (K(SV)), effective binding constant (K(A)) and corresponding dissociation constant (K(D)), binding site number (n) and binding distance (r) were obtained. The results show that these Amantadine Schiff-Bases can obviously bind to BSA molecules and the binding strength order is AS

Detection of reactive oxygen species (ROS) generated by TiO2(R), TiO2(R/A) and TiO2(A) under ultrasonic and solar light irradiation and application in degradation of organic dyes.

In the present work, the rutile, anatase and mixed (rutile and anatase) crystal phase TiO(2) powders were irradiated by ultrasound and solar light, respectively, and the generation of reactive oxygen species (ROS) were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). The DPCO can be extracted by the mixed solvent of benzene and carbon tetrachloride and the extract liquors display an obvious absorption peak around 563nm. In addition, the influences of (ultrasonic or solar light) irradiation time, TiO(2) addition amount and DPCI concentration on the quantities of generated ROS were also reviewed. The kinds of generated ROS were determined by using several radical scavengers. At last, the researches on the sonocatalytic and photocatalytic degradation of several organic dyes were also performed. It is wished that this paper might offer some important subjects for broadening the applications of sonocatalytic and photocatalytic technologies.

Spectroscopic studies on interaction and sonodynamic damage of metallochlorophyllin (Chl-M (M=Fe, Zn and Cu)) to protein under ultrasonic irradiation.

In this paper, the chlorophyll derivatives, metallochlorophyllin (Chl-M) (M=Fe, Zn and Cu) including chlorophyllin iron (Chl-Fe), chlorophyllin zinc (Chl-Zn) and chlorophyllin copper (Chl-Cu), were adopted as sonosensitizers to combine with ultrasonic irradiation, and the sonodynamic damage of bovine serum albumin (BSA) was investigated. At first, the interaction of Chl-M with BSA was studied by fluorescence spectroscopy. The results show that the quenching mechanism belongs to a static process and among them the affinity of Chl-Fe to BSA is the most obvious. Then, some influence factors on the sonodynamic damage of BSA molecules in the presence of Chl-M under ultrasonic irradiation were also studied. Synchronous fluorescence spectra show that the binding and damage sites of Chl-M to BSA molecule are mainly on the tryptophan (Trp) residues. The generation of ROS in Chl-M sonodynamic process is estimated by the method of Oxidation-Extraction Spectrometry (OEP). This paper may offer some valuable references for the study of the sonodynamic activity of Chl-M and the effect of the central metals. Synchronously, it contributes to the application of Chl-M in SDT for tumor treatment.

Oxidation-extraction spectrometry of reactive oxygen species (ROS) generated by chlorophyllin magnesium (Chl-Mg) under ultrasonic irradiation.

In order to examine the mechanism and process of sonodynamic reaction, the chlorophyllin magnesium (Chl-Mg) acting as a sonosensitizer was irradiated by ultrasound, and the generation of reactive oxygen species (ROS) were detected by the method of oxidation-extraction spectrometry (OES). That is, under ultrasonic irradiation in the presence of Chl-Mg, the 1,5-diphenyl carbazide (DPCI) is oxidized by generated ROS into 1,5-diphenyl carbazone (DPCO), which can be extracted by mixed organic solvent and display a obvious visible absorption at 563 nm wavelength. Besides, the generation conditions of ROS were also reviewed. The results demonstrated that the quantities of generated ROS increased with the increase of ultrasonic irradiation time, Chl-Mg concentration and DPCI concentration. Finally, several radical scavengers (l-Histidine (His), 2,6-Di-tert-butyl-methylphenol (BHT) and Vitamin C (VC)) were used to determine the kind of the generated ROS. It was found that at least the hydroxyl radical (OH) and singlet oxygen (1O2) were generated in the presence of Chl-Mg under ultrasonic irradiation. It is wish that this paper might offer some valuable references for the study on the mechanism of SDT and the application of Chl-Mg in tumor treatment.

Spectroscopic analyses on interaction of o-Vanillin-D-Phenylalanine, o-Vanillin-L-Tyrosine and o-Vanillin-L-Levodopa Schiff Bases with bovine serum albumin (BSA).

In this work, three o-Vanillin Schiff Bases (o-VSB: o-Vanillin-D-Phenylalanine (o-VDP), o-Vanillin-L-Tyrosine (o-VLT) and o-Vanillin-L-Levodopa (o-VLL)) with alanine constituent were synthesized by direct reflux method in ethanol solution, and then were used to study the interaction to bovine serum albumin (BSA) molecules by fluorescence spectroscopy. Based on the fluorescence quenching calculation, the bimolecular quenching constant (K(q)), apparent quenching constant (K(sv)), effective binding constant (K(A)) and corresponding dissociation constant (K(D)) as well as binding site number (n) were obtained. In addition, the binding distance (r) was also calculated according to Foster's non-radioactive energy transfer theory. The results show that these three o-VSB can efficiently bind to BSA molecules, but the binding array order is o-VDP-BSA>o-VLT-BSA>o-VLL-BSA. Synchronous fluorescence spectroscopy indicates that the o-VDP is more accessibility to tryptophan (Trp) residues of BSA molecules than to tyrosine (Tyr) residues. Nevertheless, the o-VLT and o-VLL are more accessibility to Tyr residues than to Trp residues.

Detection and comparison of reactive oxygen species (ROS) generated by chlorophyllin metal (Fe, Mg and Cu) complexes under ultrasonic and visible-light irradiation.

In this paper, in order to examine the mechanisms of sonodynamic and photodynamic reactions, the chlorophyllin metal (Chl-M (M=Fe, Mg and Cu)) complexes were irradiated by ultrasound (US) and visible-light (VL), respectively, and the generation of reactive oxygen species (ROS) were detected by the method of Oxidation-Extraction Spectrometry (OES). That is, the 1,5-diphenyl carbazide (DPCI) is oxidized by the generated ROS into 1,5-diphenyl carbazone (DPCO), which can display a various visible absorption around 563 nm wavelength. Besides, some influence parameters on the generation of ROS were also reviewed. The results demonstrated an apparent synergistic effect of Chl-M and ultrasonic or visible-light irradiation for the generation of ROS. Moreover, the quantities of generated ROS increase with the increase of (ultrasonic or visible-light) irradiation time and Chl-M (M=Fe, Mg and Cu) concentration. Finally, several quenchers were used to determine the kind of the generated ROS. It is wished that this paper might offer some valuable references for the study on the sonodynamic therapy (SDT) and photodynamic therapy (PDT) mechanisms and the application of Chl-M in tumor treatment.

Detection and analysis of reactive oxygen species (ROS) generated by nano-sized TiO2 powder under ultrasonic irradiation and application in sonocatalytic degradation of organic dyes.

Recently, the sonocatalytic technology using various semiconductors combined with ultrasonic irradiation has been received much attention to solve the environmental problems. In this paper, nano-sized titanium dioxide (TiO(2)) powder as a sonocatalyst was irradiated by ultrasound and the generation of reactive oxygen species (ROS) during sonocatalytic reaction process has been estimated by the method of Oxidation-Extraction Photometry (OEP). That is, the 1,5-diphenylcarbohydrazide (DPCI) can be oxidized by ROS into diphenylcarbonzone (DPCO), which can be extracted by the mixed solution of benzene and carbon tetrachloride and show the great absorbance at 563 nm wavelength. The synergistic effect of TiO(2) and ultrasonic irradiation was estimated and some influencing factors, such as ultrasonic irradiation time and TiO(2) addition amount on the generation of ROS were reviewed. The results indicate that the quantities of generated ROS increase with the increase of ultrasonic irradiation time and TiO(2) addition amount. Moreover, the relationship between quantities of generated ROS and DPCI concentration was also studied. And then, several quenchers were used to determine the kind of the generated ROS. At last, the researches on the sonocatalytic degradation of organic dyes and the corresponding reaction kinetics have also been performed, which is found to follow the pseudo first-order kinetics approximately. This paper may offer some important subjects for broadening the applications of sonocatalytic technology.