Highly sensitive and selective detection of amoxicillin using molecularly imprinted ratiometric fluorescent nanosensor based on quantum dots.

A dual-emission ratiometric fluorescence sensor (CDs@CdTe@MIP) with a self-calibration function was successfully constructed for AMO detection. In the CDs@CdTe@MIP system, non-imprinted polymer-coated CDs and molecule-imprinted polymer-coated CdTe quantum dots were used as the reference signal and response elements, respectively. The added AMO quenched the fluorescence of the CdTe quantum dots, whereas the fluorescence intensity of the CDs remained almost unchanged. The AMO concentration was monitored using the fluorescence intensity ratio (log(I647/I465)0/(I647/I465)) to reduce interference from the testing environment. The sensor with a low detection limit of 0.15 µg/L enabled detection of the AMO concentration within 6 min. The ratiometric fluorescence sensor was used to detect AMO in spiked pork samples; it exhibited a high recovery efficiency and relative standard deviation (RSD) of 97.94-103.70% and 3.77-4.37%, respectively. The proposed highly sensitive and selective platform opens avenues for sensitive, reliable, and rapid determination of pharmaceuticals in the environment and food safety monitoring using ratiometric sensors.

Microbial Fabrication of Quantum Dots: Mechanism and Applications.

More recently, the application of semiconductor nanomaterials called quantum dots (QDs), has gained considerable attention as they possess tunable optoelectronic and physicochemical properties. There are several routes of QDs synthesis some of which include lithography, molecular beam epitaxy, and chemical reduction. However, most of these methods are expensive, labour intensive, and produce toxic by-products. Hence, the biosynthesis of QDs has been extensively researched for addressing the issues. This review elaborates on the biogenic synthesis of cadmium selenide, cadmium telluride, cadmium sulfide, lead sulfide, and zinc sulfide QDs using bacteria, and fungi. Further, we attempt to identify the underlying mechanism and critical parameters that can control the synthesis of QDs. Eventually, their application in detectors, photovoltaics, biodiesel, photocatalysis, infection-control, and bioimaging are discussed. Thus, biogenic QDs have a tremendous scope in future to emerge as next generation nanotheranostics although thorough pharmacokinetic, and pharmacodynamic studies are required.

CRISPR-Enhanced Photocurrent Polarity Switching for Dual-lncRNA Detection Combining Deep Learning for Cancer Diagnosis.

Abnormal expression in long noncoding RNAs (lncRNAs) is closely associated with cancers. Herein, a novel CRISPR/Cas13a-enhanced photocurrent-polarity-switching photoelectrochemical (PEC) biosensor was engineered for the joint detection of dual lncRNAs, using deep learning (DL) to assist in cancer diagnosis. After target lncRNA-activated CRISPR/Cas13a cleaves to induce DNAzyme bidirectional walkers with the help of cofactor Mg2+, nitrogen-doped carbon-Cu/Cu2O octahedra are introduced into the biosensor, producing a photocurrent in the opposite direction of CdS quantum dots (QDs). The developed PEC biosensor shows high specificity and sensitivity with limits of detection down to 25.5 aM for lncRNA HOTAIR and 53.1 aM for lncRNA MALAT1. More importantly, this platform for the lncRNA joint assay in whole blood can successfully differentiate cancers from healthy people. Furthermore, the DL model is applied to explore the potential pattern hidden in data of the established technology, and the accuracy of DL cancer diagnosis can acquire 93.3%. Consequently, the developed platform offers a new avenue for lncRNA joint detection and early intelligent diagnosis of cancer.

Which Constituents Determine the Antioxidant Activity and Cytotoxicity of Garlic? Role of Organosulfur Compounds and Phenolics.

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.

Asymmetric Sulfoxidations Catalyzed by Bacterial Flavin-Containing Monooxygenases.

Flavin-containing monooxygenase from Methylophaga sp. (mFMO) was previously discovered to be a valuable biocatalyst used to convert small amines, such as trimethylamine, and various indoles. As FMOs are also known to act on sulfides, we explored mFMO and some mutants thereof for their ability to convert prochiral aromatic sulfides. We included a newly identified thermostable FMO obtained from the bacterium Nitrincola lacisaponensis (NiFMO). The FMOs were found to be active with most tested sulfides, forming chiral sulfoxides with moderate-to-high enantioselectivity. Each enzyme variant exhibited a different enantioselective behavior. This shows that small changes in the substrate binding pocket of mFMO influence selectivity, representing a tunable biocatalyst for enantioselective sulfoxidations.

Potential of Anti-Leukotriene Drugs as New Therapeutic Agents for Inhibiting Cholangiocarcinoma Progression.

Cholangiocarcinoma (CCA) is a cancer with a poor prognosis due to difficulties in diagnosis and limited treatment options, highlighting the urgent need for new targeted therapies. In a clinical setting, we found that leukotriene levels in bile were higher than in serum. Immunohistochemical analysis of surgically resected samples also revealed that CysLT receptor 1 (CysLTR1) was more highly expressed in CCA than in normal bile duct tissue, prompting us to investigate leukotriene as a potential therapeutic target in CCA. In vitro studies using CCA cell lines expressing CysLTR1 showed that leukotriene D4, a major ligand of CysLTR1, promoted cell proliferation, with increased phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Additionally, treatment with two clinically available anti-allergic drugs-zileuton, an inhibitor of CysLT formation, and montelukast, a CysLTR1 inhibitor-had inhibitory effects on cell proliferation and migratory capacity, accompanied by the reduced phosphorylation of AKT and ERK1/2. Furthermore, the simultaneous administration of both drugs synergistically enhanced the inhibitory effect on cell proliferation. Our study suggests that use of these drugs may represent a novel approach to treat CCA through drug repositioning.

Role of sulfidogenic members of the gut microbiota in human disease.

The human gut flora comprises a dynamic network of bacterial species that coexist in a finely tuned equilibrium. The interaction with intestinal bacteria profoundly influences the host's development, metabolism, immunity, and overall health. Furthermore, dysbiosis, a disruption of the gut microbiota, can induce a variety of diseases, not exclusively associated with the intestinal tract. The increased consumption of animal protein, high-fat and high-sugar diets in Western countries has been implicated in the rise of chronic and inflammatory illnesses associated with dysbiosis. In particular, this diet leads to the overgrowth of sulfide-producing bacteria, known as sulfidogenic bacteria, which has been linked to inflammatory bowel diseases and colorectal cancer, among other disorders. Sulfidogenic bacteria include sulfate-reducing bacteria (Desulfovibrio spp.) and Bilophila wadsworthia among others, which convert organic and inorganic sulfur compounds to sulfide through the dissimilatory sulfite reduction pathway. At high concentrations, sulfide is cytotoxic and disrupts the integrity of the intestinal epithelium and mucus barrier, triggering inflammation. Besides producing sulfide, B. wadsworthia has revealed significant pathogenic potential, demonstrated in the ability to cause infection, adhere to intestinal cells, promote inflammation, and compromise the integrity of the colonic mucus layer. This review delves into the mechanisms by which taurine and sulfide-driven gut dysbiosis contribute to the pathogenesis of sulfidogenic bacteria, and discusses the role of these gut microbes, particularly B. wadsworthia, in human diseases.

Copper Is Accumulated as Copper Sulfide Particles, and Not Bound to Glutathione, Phytochelatins or Metallothioneins, in the Marine Alga Ulva compressa (Chlorophyta).

To analyze the mechanism of copper accumulation in the marine alga Ulva compressa, it was cultivated with 10 µM of copper, with 10 µM of copper and increasing concentrations of a sulfide donor (NaHS) for 0 to 7 days, and with 10 µM of copper and a concentration of the sulfide acceptor (hypotaurine) for 5 days. The level of intracellular copper was determined as well as the level of glutathione (GSH) and phytochelatins (PCs) and the expression of metallothioneins (UcMTs). The level of intracellular copper in the algae treated with copper increased at day 1, slightly increased until day 5 and remained unchanged until day 7. The level of copper in the algae cultivated with copper and 100 or 200 µM of NaHS continuously increased until day 7 and the copper level was higher in the algae cultivated with 200 µM of NaHS compared to 100 µM of NaHS. In contrast, the level of intracellular copper decreased in the algae treated with copper and hypotaurine. The level of intracellular copper did not correlate with the level of GSH or with the expression of UcMTs, and PCs were not detected in response to copper, or copper and NaHS. Algae treated with copper and with copper and 200 µM of NaHS for 5 days were visualized by TEM and the elemental composition of electrondense particles was analyzed by EDXS. The algae treated with copper showed electrondense particles containing copper and sulfur, but not nitrogen, and they were mainly located in the chloroplast, but also in the cytoplasm. The algae treated with copper and NaHS showed a higher level of electrondense particles containing copper and sulfur, but not nitrogen, and they were located in the chloroplast, and in the cytoplasm. Thus, copper is accumulated as copper sulfide insoluble particles, and not bound to GSH, PCs or UcMTs, in the marine alga U. compressa.

Enhanced removal of 1,2-dichloroethane by nanoscale calcium peroxide activation with Fe(III) coupled with different iron sulfides.

Fe(II) is of great importance in iron-based advanced oxidation processes. However, traditional methods to maintain Fe(II) concentration, such as the addition of chelating agents or reducing agents, may lead to an increase in chemical oxygen demand of secondary pollution. Therefore, in this study, iron sulfides, namely ferrous sulfide (FeS), pyrite (FeS2), and sulfidated nanoscale zero-valent iron (S-nZVI), were applied for not only the regeneration of Fe(II) but also the direct dissolution of Fe(II). Nanoscale calcium peroxide (nCaO2) was synthesized and used as the oxidant. The removal of 1,2-dichloroethane (1,2-DCA) were significantly promoted from 8.8 to 98.2, 79.2, and 80.8% with the aid of FeS, FeS2, and S-nZVI within 180 min, respectively. The dominant reactive oxygen species were demonstrated and their steady-state concentrations were quantified. Besides, the dechlorination of 1,2-DCA reached 90.4, 69.5, and 83.9% in nCaO2/Fe(III) systems coupled with FeS, FeS2, and S-nZVI, respectively. All three systems had high tolerance to the complex water conditions, of which FeS-enhanced nCaO2/Fe(III) system displayed the best performance, which could be recommended to put into practice for the remediation of 1,2-DCA contaminated groundwater.

Lavandula angustifolia Essential Oil Inhibits the Ability of Fusobacterium nucleatum to Produce Volatile Sulfide Compounds, a Key Components in Oral Malodor.

Oral malodor still constitutes a major challenge worldwide. A strong effort is invested in eliminating volatile sulfur compound-producing oral bacteria through organic natural products such as essential oils. Fusobacterium nucleatum is a known volatile sulfur compound-producing bacteria that inspires oral malodor. The aim of the present study was to test the effect of lavender essential oil on the bacterium's ability to produce volatile sulfide compounds, the principal components of oral malodor. Lavender (Lavandula angustifolia) essential oil was extracted by hydrodistillation and analyzed using GC-MS. The minimal inhibitory concentration (MIC) of lavender essential oil on Fusobacterium nucleatum was determined in a previous trial. Fusobacterium nucleatum was incubated anaerobically in the presence of sub-MIC, MIC, and above MIC concentrations of lavender essential oil, as well as saline and chlorhexidine as negative and positive controls, respectively. Following incubation, volatile sulfur compound levels were measured using GC (Oralchroma), and bacterial cell membrane damage was studied using fluorescence microscopy. Chemical analysis of lavender essential oil yielded five main components, with camphor being the most abundant, accounting for nearly one-third of the total lavender essential oil volume. The MIC (4 µL/mL) of lavender essential oil reduced volatile sulfur compound secretion at a statistically significant level compared to the control (saline). Furthermore, the level of volatile sulfur compound production attributed to 1 MIC of lavender essential oil was in the range of the positive control chlorhexidine with no significant difference. When examining bacterial membrane damage, 2 MIC of lavender essential oil (i.e., 8 µL/mL) demonstrated the same, showing antibacterial membrane damage values comparative to chlorhexidine. Since lavender essential oil was found to be highly effective in hindering volatile sulfur compound production by Fusobacterium nucleatum through the induction of bacterial cell membrane damage, the results suggest that lavender essential oil may be a suitable alternative to conventional chemical-based anti-malodor agents.

NaHS immersion alleviates the stress effect of chromium(III) on alfalfa seeds by affecting active oxygen metabolism.

OBJECTIVE: This study aimed to investigate the regulatory effects of exogenous hydrogen sulfide (H2S) on seed germination, seedling growth, and reactive oxygen species (ROS) homeostasis in alfalfa under chromium (Cr) ion (III) stress. METHODS: The effects of 0-4 mM Cr(III) on the germination and seedling growth of alfalfa were first assessed. Subsequently, following seed NaHS immersion, the influence of H2S on alfalfa seed germination and seedling growth under 2 mM Cr(III) stress was investigated, and the substance contents and enzyme activities associated with ROS metabolism were quantified. RESULTS: Compared to the control group, alfalfa plant germination was delayed under 2 mM Cr(III) stress for up to 48 h (p < 0.05). At 120 h, the total seedling length was approximately halved, and the root length was roughly one-third of the control. Treatment with 0.02-0.1 mM NaHS alleviated the delay in germination and root growth inhibition caused by 2 mM Cr(III) stress, resulting in an increased ratio of root length to hypocotyl length from 0.57 to 1 above. Additionally, immersion in 0.05 mM NaHS reduced hydrogen peroxide (H2O2) and oxygen-free radicals (O2· -) levels (p < 0.05), boosted glutathione (GSH) levels (p < 0.05), and notably enhanced catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) activities (p < 0.05) compared to the 2 mM Cr(III) stress treatment group. CONCLUSION: Seed immersion in NaHS mitigated the delay in germination and inhibition of root elongation under 2 mM Cr(III) stress. This effect is likely attributed to the regulation of intracellular ROS homeostasis and redox balance through enzymatic and non-enzymatic systems; thus, providing a potential mechanism for combating oxidative stress.

Modelling anaerobic sulfide removal by sulfide shuttling bacteria.

Sulfide oxidizing bacteria are used in industrial biodesulfurization processes to convert sulfide to sulfur. These bacteria can spatially separate sulfide removal from terminal electron transfer, thereby acting as sulfide shuttles. The mechanisms underlying sulfide shuttling are not yet clear. In this work, newly obtained sulfide removal data were used to develop a new model for anaerobic sulfide removal and this model was shown to be an improvement over two previously published models. The new model describes a fast chemical step and a consecutive slow enzymatic step. The improved model includes the effect of pH, with higher total sulfide removal at increasing pH, as well as partial sulfide removal at higher sulfide concentrations. The two-stage model is supported by recent developments in anaerobic sulfide removal research and contributes to a better understanding of the underlying mechanisms. The model is a step toward accurately modelling anaerobic sulfide removal in industrial systems.

Predictive and therapeutic value of lipoprotein-associated phospholipaseA2 in sarcopenia in chronic obstructive pulmonary disease.

BACKGROUND: Sarcopenia, characterized by progressive muscle dysfunction, is a common complication of chronic obstructive pulmonary disease (COPD). Our previous study revealed serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2) level significantly increased in COPD and associated with exercise tolerance. This study further investigated the functions and target potential of Lp-PLA2 for sarcopenia in COPD. METHODS: The circulating Lp-PLA2 level/enzyme activity in COPD patients and age-matched healthy volunteers were measured. Clinical parameters on skeletal muscle were measured and their correlations with Lp-PLA2 were analyzed. We explored the involvement of Lp-PLA2 in vivo and treatment effectiveness of darapladib (a specific Lp-PLA2 inhibitor) in CS-induced muscle dysfunction models. RESULTS: Circulating Lp-PLA2 level/enzyme activity was elevated in COPD patients compared with healthy controls, negatively associated with skeletal muscle mass and function. In CS-induced muscle dysfunction murine models, up-regulated serum Lp-PLA2 level/enzyme activity was verified again. In CS-exposed mouse models, darapladib treatment reversed muscle mass loss and muscle dysfunction, meanwhile rescued upregulation of MuRF1 and atrogin-1, and activation of inflammatory factors, oxidant enzymes and NF-κB signaling. CONCLUSIONS: Lp-PLA2 could be a potential indicator for sarcopenia in COPD. Darapladib, a Lp-PLA2 inhibitor, can alleviate CS-induced skeletal muscle dysfunction and represents a potential therapeutic for sarcopenia in COPD.

Visualization of 2D and 3D Tissue Models via Size-Selected Aqueous AgInS/ZnS Quantum Dots.

Three-dimensional (3D) spheroid cell cultures of fibroblast (L929) and tumor mammary mouse (4T1) were chosen as in vitro tissue models for tissue imaging of ternary AgInS/ZnS fraction quantum dots (QDs). We showed that the tissue-mimetic morphology of cell spheroids through well-developed cell-cell and cell-matrix interactions and distinct diffusion/transport characteristics makes it possible to predict the effect of ternary AgInS/ZnS fraction QDs on the vital activity of cells while simultaneously comparing with classical two-dimensional (2D) cell cultures. The AgInS/ZnS fractions, emitting in a wide spectral range from 635 to 535 nm with a mean size from ∼3.1 ± 0.8 to ∼1.8 ± 0.4 nm and a long photoluminescence lifetime, were separated from the initial QD ensemble by using antisolvent-induced precipitation. For ternary AgInS/ZnS fraction QDs, the absence of toxicity at different QD concentrations was demonstrated on 2D and 3D cell structures. QDs show a robust correlation between numerous factors: their sizes in biological fluids over time, penetration capabilities into 2D and 3D cell structures, and selectivity with respect to penetration into cancerous and healthy cell spheroids. A reproducible protocol for the preparation of QDs along with their unique biological properties allows us to consider ternary AgInS/ZnS fraction QDs as attractive fluorescent contrast agents for tissue imaging.

One-Pot Synthesis of Glutathione Trisulfide from Oxidized Glutathione.

The excellent medicinal efficacy of glutathione trisulfide, an endogenous compound consisting of sulfane sulfur and two molecules of reduced glutathione, has been reported in recent years. However, no efficient procedure for the synthesis of trisulfide is yet available. Herein, we investigated the optimal conditions for the oxidation reaction of oxidized glutathione to thiosulfinate and its subsequent trisulfidation reaction using commercially available materials. The optimized one-pot reactions enabled the isolation of glutathione trisulfide dihydrate by crystallization on a 20 g scale in high yield (up to 74% for the two steps, >95% purity). Liquid chromatography-mass spectrometry/MS (LC-MS/MS) measurements using Na234S as a sulfur source revealed that 34S was inserted only into the center of the trisulfide with high selectivity (>99% enrichment) during the reaction. The reaction mechanism indicated that disulfide bonds were cleaved by the reaction of thiosulfinate and a sulfur source, followed by trisulfide bond-formation via the dehydration condensation of sulfenic acid and persulfide.

Enzymatically Mediated In Situ Generation of Z-Scheme Bi2S3/Bi2MoO6 Heterojunction-Based Organic Photoelectrochemical Transistor for METTL3/METTL14 Detection.

The OPECT biosensing platform, which connects optoelectronics and biological systems, offers significant amplification and more possibilities for research in biological applications. In this work, a homogeneous organic photoelectrochemical transistor (OPECT) biosensor based on a Bi2S3/Bi2MoO6 heterojunction was constructed to detect METTL3/METTL14 protein activity. The METTL3/METTL14 complex enzyme was used to catalyze adenine (A) on an RNA strand to m6A, protecting m6A-RNA from being cleaved by an E. coli toxin (MazF). Alkaline phosphatase (ALP) catalyzed the conversion of Na3SPO3 to H2S through an enzymatic reaction. Due to the adoption of the strategy of no fixation on the electrode, the generated H2S was easy to diffuse to the surface of the ITO electrode. The Bi2S3/Bi2MoO6 heterojunction was formed in situ through a chemical replacement reaction with Bi2MoO6, improving photoelectric conversion efficiency and realizing signal amplification. Based on this "signal on" mode, METTL3/METTL14 exhibited a wide linear range (0.00001-25 ng/µL) between protein concentration and photocurrent intensity with a limit of detection (LOD) of 7.8 fg/µL under optimal experimental conditions. The applicability of the developed method was evaluated by investigating the effect of four plasticizers on the activity of the METTL3/METTL14 protein, and the molecular modeling technique was employed to investigate the interaction between plasticizers and the protein.

Photoelectrochemical/Colorimetric Dual-Mode Specific Detection of Staphylococcus aureus Based on the Enzymatic Reaction Triggered by Catalase from Lysed Bacteria.

Staphylococcus aureus (S. aureus) is abundant in nature and frequently leads to various health issues. Bacteriophages as obligate intracellular parasites of bacteria have the ability to specifically identify and infect S. aureus, causing bacterial lysis and the release of endogenous catalase (CAT). The released CAT triggers the conversion of H2O2 into O2 and H2O, resulting in a notable decrease in UV absorption at 570 nm and a concurrent surge in photocurrent. On the basis of this, a photoelectrochemical/colorimetric dual-mode biosensor for the detection of S. aureus was developed. In the photoelectric detection mode, the reactions involving endogenous enzymes occur directly in the solution, requiring only the simple drop-coating of TiO2@CdS onto the indium tin oxide (ITO) electrode surface. There was no need for immobilizing additional biomolecules, thereby significantly minimizing nonspecific adsorption and improving the biosensor's stability and reproducibility. For colorimetry, we utilized a cost-effective and operationally simple approach based on KI and starch. Remarkably, this photoelectrochemical/colorimetry exhibited a linear range of 102-109 CFU/mL for S. aureus, achieving detection limits of 7 and 10 CFU/mL, respectively. Herein, phage identification ensures the specific detection of live S. aureus, thereby effectively mitigating the potential for false signals. The dual-signal readout mode improves the detection accuracy and reliability. In conclusion, this present method offers numerous advantages, including simplicity, time-efficiency, cost-effectiveness, high specificity, and therefore excellent accuracy.

Metagenomics and Stable Isotopes Uncover the Augmented Sulfide-Driven Autotrophic Denitrification in a Seasonally Hypoxic, Sulfate-Abundant Reservoir.

The mechanism governing sulfur cycling in nitrate reduction within sulfate-rich reservoirs during seasonal hypoxic conditions remains poorly understood. This study employs nitrogen and oxygen isotope fractionation in nitrate, along with metagenomic sequencing to elucidate the intricacies of the coupled sulfur oxidation and nitrate reduction process in the water column. In the Aha reservoir, a typical seasonally stratified water body, we observed the coexistence of denitrification, bacterial sulfide oxidation, and bacterial sulfate reduction in hypoxic conditions. This is substantiated by the presence of abundant N/S-related genes (nosZ and aprAB/dsrAB) and fluctuations in N/S species. The lower 15εNO3/18εNO3 ratio (0.60) observed in this study, compared to heterotrophic denitrification, strongly supports the occurrence of sulfur-driven denitrification. Furthermore, we found a robust positive correlation between the metabolic potential of bacterial sulfide oxidation and denitrification (p < 0.05), emphasizing the role of sulfide produced via sulfate reduction in enhancing denitrification. Sulfide-driven denitrification relied on ∑S2- as the primary electron donor preferentially oxidized by denitrification. The pivotal genus, Sulfuritalea, emerged as a central player in both denitrification and sulfide oxidation processes in hypoxic water bodies. Our study provides compelling evidence that sulfides assume a critical role in regulating denitrification in hypoxic water within an ecosystem where their contribution to the overall nitrogen cycle was previously underestimated.

Protective effect of leukotriene receptor antagonist, montelukast, against cyclophosphamide-induced placental toxicity via modulation of NLRP3/IL-1ß signaling pathway in rats.

BACKGROUNDS & AIM: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats. MATERIALS AND METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1ß (IL-1ß), and cleaved caspase-3 immuno-expressions were also evaluated. RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1ß and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1ß), and apoptotic (caspase-3) parameters. CONCLUSION: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1ß signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.

Ultrasensitive Photoelectrochemical Biosensor for Dual-miRNAs Detection Based on Molecular Logic Gates and Methylene Blue Sensitized ZnO@CdS@Au Nanorods.

The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the input signals and logical operations of DNA logic gates, detection and diagnosis of cancer at different stages can be achieved. For example, in the early stages, specific input signals can be designed to correspond to early specific tumor markers, thereby achieving early cancer detection. In the late stage, logic gates for multitarget detection can be designed to simultaneously detect multiple biomarkers to improve diagnostic accuracy and comprehensiveness. In this work, we constructed a dual-target-triggered DNA logic gate for anchoring DNA tetrahedra, where methylene blue was embedded in the DNA tetrahedra to sensitize ZnO@CdS@Au, achieving ultrasensitive detection of the target substance. We tested the response of AND and OR logic gates to the platform. For AND logic gates, the sensing platform only responds when both miRNAs are present. In the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. Subsequently, we used OR logic gates for miRNA detection. Even if only one target exists, the sensing platform exhibits excellent performance. Similarly, within the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. The minimum detection limit is 1.10 aM. Whether it is the need to detect multiple targets simultaneously or only one of them, we can achieve it by selecting the appropriate logic gate. This strategy holds promising application prospects in fields such as biosensing, medical diagnosis, and environmental monitoring.