Potential negative effect of long-term exposure to nitrofurans on bacteria isolated from wastewater.

Nitrofurans are broad-spectrum bactericidal agents used in a large quantity for veterinary and human therapy. This study reports the long-term impact of two nitrofuran representatives, nitrofurantoin (NFT) and furaltadone (FTD) on the bacterial strains Sphingobacterium siyangense FTD2, Achromobacter pulmonis NFZ2, and Stenotrophomonas maltophilia FZD2, isolated from a full-scale wastewater treatment plant. Bacterial whole genome sequencing was used for preliminary strains characterization. The metabolomic, electrochemical, and culture methods were applied to understand changes in the bacterial strains after 12-month exposure to nitrofurans. The most significantly altered metabolic pathways were observed in amino acid and sugar metabolism, and aminoacyl-tRNA biosynthesis. Disrupted protein biosynthesis was measured in all strains treated with antibiotics. Prolonged exposure to NFT and FTD also triggered mutagenic effects, affected metabolic activity, and facilitated oxidative stress within the cells. Nitrofuran-induced oxidative stress was evidenced from an elevated activity of catalase and glutathione S-transferases. NFT and FTD elicited similar but not identical responses in all analyzed strains. The results obtained in this study provide new insights into the potential risks of the prolonged presence of antimicrobial compounds in the environment and contribute to a better understanding of the possible impacts of nitrofuran antibiotics on the bacterial cells.

Facile synthesis of triazine-based porous organic polymer for the extraction and determination of nitrofuran metabolites residues from meat samples with ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry.

In this work, a novel triazine-based porous organic polymers, TAPT-BPDD, was firstly synthesized by a facile method at room temperature. After characterized by FT-IR, FE-SEM, XRPD, TGA, and nitrogen-sorption experiments, TAPT-BPDD was applied as solid-phase extraction (SPE) adsorbent for the extraction of four trace nitrofuran metabolites (NFMs) from meat samples. The key parameters including the adsorbent dosage, sample pH, type and volume of eluents, type of washing solvents were evaluated in the extraction process. Combined with ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) analysis, good linear relationship (1-50 µg·kg-1, R2>0.9925) and low limits of detection (LODs, 0.05-0.56 µg·kg-1) were obtained under the optimal conditions. When spiked at different level, the recoveries were in the range of 72.7-111.6%. The adsorption isothermal model and extraction selectivity of TAPT-BPDD were also studied in detail. The results showed that TAPT-BPDD was a kind of promising SPE adsorbent for the enrichment of organics in food samples.

Nifuroxazide Activates the Parthanatos to Overcome TMPRSS2:ERG Fusion-Positive Prostate Cancer.

Fusion of the E-26 transformation-specific (ETS)-related gene (ERG) with transmembrane serine protease 2 (TMPRSS2) is a crucial step in the occurrence and progression of approximately 50% of prostate cancers. Despite significant progress in drug discovery, ERG inhibitors have yet to be approved for the clinical treatment of prostate cancer. In this study, we used computer-aided drug design (CADD)-based virtual screening to screen for potential inhibitors of ERG. In vivo and in vitro methods revealed that nifuroxazide (NFZ) inhibited the proliferation of a TMPRSS2:ERG fusion-positive prostate cancer cell line (VCaP) with an IC50 lower than that of ERG-negative prostate cancer cell lines (LNCaP, DU145, and WPMY cells). Poly [ADP-ribose] polymerase 1, the critical mediator of parthanatos, is known to bind ERG and is required for ERG-mediated transcription. NFZ blocked this interaction and overly activated PARP1, leading to cell death that was reduced by olaparib, a PARP1 inhibitor. These results show that NFZ inhibits ERG, leading to parthanatic cell death.

Simultaneous determination of five metabolites of nitrofurans including the metabolite nifursol in shrimp and fish by UPLC- MS/MS: in-house method validation according to commission implementing regulation (EU) 2021/808.

For the simultaneous identification and quantification of five nitrofurans metabolites in farmed shrimp and fish, 3-amino-2-oxazolidinone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), 1-aminohydantoine (AHD), semicarbazide (SEM), and 3,5-dinitrosalicylic acid hydrazide (DNSH), an accurate, precise, and specific method was developed. The mixture of water and methanol (60/40; v/v) was found to be the final optimised solvent for injection. The analytical run duration was 7 min, and the mobile phase included 2 mM methanol and ammonium formate. The new reference point for action (RPA) of 0.50 µg kg-1 as per EC/1871/2019 was taken into consideration and evaluated for the performance characteristics as per the CIR (EC)/2021/808 criteria. Specificity, relative retention time (≤0.25%) relative ion ratio (≤40%), linearity (0.25 to 2.0 µg kg-1), trueness (between 82.8 and 118.1%), repeatability (RSDr ≤14%), within lab reproducibility (RSDwr ≤16.9%), CCα (0.32-0.36 µg kg-1), ruggedness and relative matrix effect (≤14.26%) achieved acceptable values.

Quantum Dot Nanobeads as Multicolor Labels for Simultaneous Multiplex Immunochromatographic Detection of Four Nitrofuran Metabolites in Aquatic Products.

A multicolor immunochromatographic assay platform based on quantum dot nanobeads (QBs) for the rapid and simultaneous detection of nitrofuran metabolites in different aquatic products is documented. These metabolites include 3-amino-2-oxazolidinone (AOZ), 1-aminohydantoin (AHD), semicarbazide (SEM), and 3-amino-5-morpholino-methyl-1,3-oxazolidinone (AMOZ). QBs with emission colors of red, yellow, green, and orange were employed and functionalized with the corresponding antibodies to each analyte to develop a multicolor channel. The visual detection limits (cutoff values) of our method for AOZ, AHD, SEM, and AMOZ reached up to 50 ng/mL, which were 2, 20, 20, and 20 times lower than those of traditional colloidal gold test strips, respectively. The test strip is capable of detection within 10 min in real samples while still achieving good stability and specificity. These results demonstrate that the developed multicolor immunochromatographic assay platform is a promising technique for multiplex, highly sensitive, and on-site detection of nitrofuran metabolites.

Current trends in analytical strategies for the chromatographic determination of nitrofuran metabolites in food samples. An update since 2012.

Nitrofurans (NFs) are synthetic broad-spectrum antibacterial and antiparasitic drugs, which recently were extensively used in veterinary practice. In the body of animals, NFs are converted into carcinogenic and mutagenic metabolites that can be accumulated in foods of animal origin having an adverse effect on human health. Therefore, NFs are currently banned in animal husbandry and aquaculture of many countries. However, the data from monitoring the quality of food products indicate that, despite the prohibitions established by the law, they still are used not only in the developing countries but also in the European Union, due to their high antibacterial activity, low cost, and accessibility. Thus, it is of great importance for human health to develop reliable and sensitive analytical methods for monitoring NF metabolites in animal-derived foods. The objective of this review is to summarize the pretreatment strategies and chromatographic methods that have been reported during the last decade for the determination of NF metabolites in food samples, and to outline the future trends with an emphasis on the novel solutions in this area.

Dual-Color 2D Lead-Organic Framework with Two-Fold Interlocking Structures for the Detection of Nitrofuran Antibiotics and 2,6-Dichloro-4-nitroaniline.

The misuse of organic pollutants such as nitrofuran antibiotics (NFAs) and 2,6-dichloro-4-nitroaniline (DCN) has become a hot topic of global concern, and developing rapid, efficient, and accurate techniques for detecting NFAs and pesticides in water is a major challenge. Here, we designed a novel lead-based anion 2D metal-organic framework (MOF){[(CH3)2NH2]2[Pb(TCBPE)(H2O)2]}n (F3) with interlocking structures, in which TCBPE stands for 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene. Powder X-ray diffraction and thermogravimetric analysis revealed that F3 has excellent chemical and solvent stability. It is worth noting that F3 has a grinding discoloration effect. The solvent-protected grinding approach achieved F3B with a high quantum yield (QY = 73.77%) and blue fluorescence, while the direct grinding method produced F3Y with a high quantum yield (QY = 37.27%) and yellow-green fluorescence. Importantly, F3B can detect NFAs in water rapidly and sensitively while remaining unaffected by other antibiotics. F3Y can identify DCN in water quickly and selectively while remaining unchanged by other pesticides. F3B demonstrated high selectivity and rapid response to NFAs at a limit of detection (LOD) as low as 0.26 µM, while F3Y indicated high selectivity and responded quickly to DCN in water at an LOD as low as 0.14 µM. The method was successfully applied to detect NFAs in actual water samples of the fish tanks and ponds as well as the pesticide DCN in soil samples. The recovery rates were 97.0-105.15% and 102.2-106.48%, and the relative standard deviations were 0.63-1.45% and 0.29-1.69%, respectively. In addition, F3B and F3Y can be made into fluorescent test papers for the visual detection of NFAs and DCN, respectively. Combined with experiments and density functional theory calculations, the mechanism of fluorescence quenching of MOFs by target analytes was also revealed.

[Rationale for choosing an antibiotic for the treatment of cystitis: recommendations of clinical pharmacologists: A review].

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

Investigation of the antimicrobial and antifungal activities of some 1,2,4-triazole derivatives.

This article presents the results of the study of the antimicrobial and antifungal properties among 1,2,4-triazole derivatives synthesized at the Department of Physical and Colloidal Chemistry of the Zaporizhzhia State Medical University. Previous studies have established the antimicrobial and antifungal activity of 1,2,4-triazole derivatives. Therefore, it was reasonable to investigate highly effective substances with antimicrobial and antifungal properties among synthesized compounds. In the first stage of our research, acute toxicity prediction was performed. The antimicrobial and antifungal properties were carried out by the method of “serial dilutions” on a liquid nutrient. Forty-seven compounds of the different classes were studied for these types of activities. According to our research, derivatives of 3-amino-1,2,4-triazole showed better performance than 3-thio-1,2.4-triazoles for Staphylococcus aureus and Candida albicans. 5-(1Н-tetrazole-1-іl)methyl-4Н- -1,2,4-triazole-3-yl-1-(5-nitrofuran-2-yl)methanimin (11.6) was showed the greatest antimicrobial and antifungal activity. Deeper research for compound 11.6 was done by diffusion in agar (method of “wells”). Studies have shown that molecule 11.6 showed antimicrobial and antifungal action to the studied test strains at a concentration of 2 μg/ml. Hence, this compound can be developed as a helpful therapeutic agent after establishing its safety pharmacology and toxicity.

The impact of provisional intraradicular retainers cementation with temporary methacrylate-based resin in the bond strength of glass fiber posts to root dentin.

Chemical composition of temporary cements interferes in the bond strength and quality of the bond interface of glass fiber posts to root dentin. The aim of the present study was to evaluate the influence of different temporary cements on the bond strength of fiberglass posts and resin cement. Thirty-two maxillary central incisor roots were standardized at 15 mm length. The root canals were prepared with Reciproc R50 and filled with a R50 single cone and AH Plus. Ten mm of filling material was removed with a heated Schilder condenser, leaving 5 mm of apical filling material. The roots were randomly distributed into 4 groups (n = 8). In the control group, the root canal was prepared with a standard drill according to the post diameter (DC #1, FGM, Joinville, Brazil), irrigated with 5 mL of distilled water and immediately received the fiberglass post cemented with self-adhesive resin cement. For the other groups, cores were made with temporary intraradicular retainers cemented with different temporary cements: methacrylate-based resin (Bifix Temp - Voco), calcium hydroxide-based (Provicol - Voco) and zinc oxide-based - eugenol-free (Relyx Temp NE - 3M). After 7 days, mechanical removal of the temporary retainers, preparation, irrigation of the root canal and cementation of the fiberglass post were performed, following the same protocol that had been performed in the control group. The roots were sectioned to obtain 3 slices per root third. The most cervical section of each third was used for the push-out test and failure pattern analysis, while the most apical section was subjected to analysis of the adhesive interface by scanning electron microscopy (SEM). The BS data were compared between groups using the two-way ANOVA and Tukey post-test. The failure pattern results were expressed in percentage and compared between groups using the chi-square test and the material adaptation data at the bond interface were evaluated using the Kruskal-Wallis and Dwass-Steel-Critchlow-Fligner tests. The results showed higher BS in the cervical third, with a higher value in the control group (10.8 ± 0.94) and Bifix Temp group (9.78 ± 0.71), with no statistically significant difference between these groups (P > .05). The middle and apical thirds showed no statistically significant difference (P > .05). As regards the type of failure, a higher percentage of mixed adhesive failures was observed for all groups. Analysis of the adhesive interface by SEM showed that the temporary cement Bifix Temp showed greater adaptation at the bond interface. It was concluded that the methacrylate-based resin temporary cement showed the highest bond strength values and best adaptation to root dentin than the zinc oxide-based and calcium hydroxide-based temporary cements.

A novel detection strategy for nitrofuran metabolite residues: Dual-mode competitive-type electrochemical immunosensor based on polyethyleneimine reduced graphene oxide/gold nanorods nanocomposite and silica-based multifunctional immunoprobe.

Excessive residues of semicarbazide (SEM) can accumulate in animals after the original drug has been abused, posing a risk to human health. Herein, based on multifunctional silica-initiated dual mode signal response, a novel competitive-type immunosensor was constructed for ultrasensitive detection of SEM. As a preliminary signal amplification platform for immunosensors, polyethyleneimine reduced graphene oxide composite gold nanorods (PEI-rGO/AuNRs) modified gold electrodes (AuE) provide a high specific surface area and high electrical conductivity. The thionine-aminated silica nanospheres-AuPt (thi-SiO2@AuPt) were synthesized by a racile coprecipitation method for enzyme immobilization and redox species loading. The multifunctional silica nanosphere conjugated with labeling antibodies (Ab2) was employed as an immunoprobe. The per unit concentration target of SEM can be determined by differential pulse voltammetry (DPV) to detect the thi loaded on the immunoprobe, which can also be determined by square wave voltammetry (SWV) to detect the current generated by the reaction system of H2O2 and hydroquinone (HQ) catalyzed by the immunoprobe with peroxidase. Under optimal conditions, the proposed immunosensor displayed a wide linear range from 1 µg-0.01 ng/mL and low detection limits (S/N = 3) of 0.488 pg/mL and 0.0157 ng/mL, respectively. Ultimately, the developed method exhibits excellent performance in practical applications, providing promising probabilities for SEM detection.

Pimitespib, an HSP90 inhibitor, augments nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop in rats with bleomycin-challenged lungs: Evolutionary perspective in managing pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a fatal lung disorder in which the etiology and pathogenesis are still unobvious. Effective treatments are urgently needed considering that lung transplantation is the only treatment that could improve outcomes. This study aimed to investigate the therapeutic significance of the dual administration of pimitespib, an HSP90 inhibitor, and nifuroxazide, a STAT3 inhibitor, against bleomycin-induced pulmonary fibrosis in rats. Our results revealed that pimitespib/nifuroxazide inhibited bleomycin-induced alterations in the structure and the function of the lungs. They demonstrated significant decreases in the BALF total and differential cell counts, LDH activity, and total protein. Concurrently, there was a reduction in the accumulation of collagen as proved by decreased hydroxyproline and the gene expression of COL1A1 accompanied by lower levels of PDGF-BB, TIMP-1, and TGF-ß. The levels of IL-6 were also downregulated. Pimitespib-induced inhibition of HSP90 led to subsequent inhibition of HIF-1α and STAT3 client proteins since the closed HSP90 would not enclose its client proteins. Therefore, pimitespib resulted in the repression of HIF-1α/CREB-p300 HAT as well as the STAT3/CREB-p300 HAT nuclear interactions. On the other hand, nifuroxazide resulted in a notable decline in pSTAT3 and HIF-1α levels. Subsequently, the combined effects of both drugs led to a substantial reduction in ECM deposition. Herein, pimitespib augmented nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop. Our findings also disclose that this novel loop is a promising therapeutic attack site for possible pulmonary fibrosis repression studies. Therefore, the use of pimitespib/nifuroxazide embodies an evolutionary perspective in managing pulmonary fibrosis.

Evaluation of anti-parasitic activities of new quinolones containing nitrofuran moiety against Toxoplasma gondii.

Toxoplasmosis is a disease with a worldwide prevalence that is caused by Toxoplasma gondii. Pyrimethamine and sulfadiazine are two pharmacological agents commonly used to treat of this infection. However, they are accompanied by some side effects. Therefore, the identifying of new drugs with low toxocytosis seems to be a matter of vital importance. Quinolones are DNA replication inhibitors, exerting inhibitory effects against many pathogens, including bacteria, mycoplasma, and protozoa. Given the importance of quinolones and their efficacy, the present in vitro study was conducted to investigate the antiparasitic activities of new quinolones (NFQ-2, NFQ-5, and NFQ-6) containing nitrofuran moiety against T. gondii. To this end, Vero cells were incubated with various concentrations of new quinolones and pyrimethamine (positive control) to determine their viability. Subsequently, they were infected with T. gondii (RH strain) and then subjected to drug treatment. The obtained IC50 values were 3.60, 4.84, 5.59, 3.44 and 2.75 µg/mL for NFQ-2, NFQ-5, NFQ-6, ciprofloxacin and pyrimethamine, respectively. The CC50 values for the NFQ-2, NFQ-5, and NFQ-6 were 25.20, 29.89, and 28.43 µg/mL, indicating the selectivity indexes more than 5 for these compounds. The anti-Toxoplasma efficiency was determined by evaluating infection index, number and size of plaques, and T. gondii intracellular proliferation. As the results indicated, the administration of new quinolone derivatives resulted in the reduction of intracellular proliferation, infection index, and the number and size of plaques in comparison to uninfected treated cells (P < 0.05). The results were indicative of a considerable synergetic effect when each of the derivatives was used in combination with pyrimethamine, compared to when used alone. Based on our results, the nitrofuran-derived quinolones can be considered as new leads for the design of new anti-Toxoplasma agents.

2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.

Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson's disease.

UV/solar photo-degradation of furaltadone in homogeneous and heterogeneous phases: Intensification with persulfate.

Previous studies on removal of the pharmaceutical drug Furaltadone (FTD) in water have not shown to be totally efficient or are very expensive. In this study, sulfate radicals derived from persulfate anions activated with different irradiation sources (UVA, UVC and solar light) and combined with H2O2 and/or TiO2 have been tested in homogeneous and heterogeneous phases under different operation modes and reaction systems. In homogeneous phase, UV produces a slow mineralization (k = 0.0013 min-1). The combined processes are faster (kUV/H2O2 = 0.0185 min-1, kUV/PS = 0.0206 min-1) with the best performance for the UV/PS system yielding nearly 80% of mineralization in half an hour. The overall process (UV/H2O2/PS) does not show synergy and mineralization is even slower (kUV/H2O2/PS = 0.015 min-1) due to the production of a high amount of radicals favouring unproductive reactions (scavenger effect). A mineralization mechanism is proposed involving formation of 5hydroxymethylene-2(5H)-furanone and NO as the main intermediates. In heterogeneous phase (UVA/TiO2/PS), the holes play an important role changing the mineralization mechanism. The main intermediates formed were C12H17N4O4 and C11H14N3O4, which rapidly were degraded to form C8H15O3N3, C4H10NO and C5H10NO. An economic study of operation costs has been made for selected processes: UVC/PS, UVA/TiO2/PS and Solar/TiO2/PS. The Solar/TiO2/PS process has the lowest operation costs due to the use of solar energy. However, it would need an additional stage to recover the catalyst. Finally, a loss of 27% in efficiency during mineralization was found after 5 cycles, but the catalyst recovers its initial performance after regeneration at 500 °C.

Nifuroxazide modulates hepatic expression of LXRs/SR-BI/CES1/CYP7A1 and LDL-R and attenuates experimentally-induced hypercholesterolemia and the associated cardiovascular complications.

Hyperlipidemia is a serious disorders affecting the metabolism of fats in the human body, and it is usually associated with some serious cardiovascular complications increasing the risk for sudden death. Nifuroxazide (NFR) is an oral nitrofuran antibiotic that has long been used for management of diarrhea and recently various recent out merging valuable therapeutic impacts were reported. The current study sought the concept of repositioning nifuroxazide in management of hyperlipidemia. Hyperlipidemia was induced in male rabbits using cholesterol enriched diet for 9 weeks and starting from the beginning of 5th week; NFR (100 and 300 mg/kg) were administered once daily for the further 5 weeks; till the end of the 9th week of the experiment. NFR significantly recovered balanced lipid profile as serum cholesterol, total glycerides, LDL significantly declined with significant elevation in serum HDL. Meanwhile, serum LDH, CK, ALT and AST activities were significantly corrected. These biochemical changes were correlated with significant improvement in the histopathological examination of hepatic, cardiac and aortic specimen with decreased expression of CD68 and Ki67 in the myocardium and the aorta implying retraction in macrophages' infiltration and tissue regeneration. Myocardial specimen confirmed significant recovery with preservation of cardiac muscle fibers. Aortic specimen confirmed retraction in the aortic thickness and fewer deposition of fat globules. In conclusion, NFR attenuated experimentally-induced hyperlipidemia with significant recovery of serum profile and tissue necrotic changes. The histopathological examination of hepatic, myocardial and aortic specimen confirmed the onset of tissues' recovery alongside biochemical improvement.

Verification of Bound Aminoguanidine as the Marker Residue for the Banned Antibiotic, Nitrovin, in Pig Tissues.

Nitrovin (NTV) belongs to a class of antibiotics called nitrofurans, which are classified as nonallowed pharmacologically active substances that do not have a maximum residue limit listed in EU legislation. The objectives of this study were to confirm aminoguanidine (AGN) as a suitable marker residue to monitor NTV abuse and to investigate its persistence in porcine tissues. In this work, pigs were fed with NTV-medicated feed (50 mg/kg), and tissues (kidney, muscle, and liver) and plasma were collected on different withdrawal days. All samples were analyzed for bound AGN, total AGN, and the parent drug NTV itself. The highest concentrations of AGN residues were found in the liver, while the lowest were in muscle. Parent NTV was only detected in the kidney at low levels on day 0 of withdrawal. The findings are in support of using AGN as the marker residue for monitoring the illegal use of NTV in animal-derived products.

Nifuroxazide in combination with CpG ODN exerts greater efficacy against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumour in China that remains a major challenge to the medical community, and effective treatment is urgently needed. Due to complex tumorigenesis, monotherapy shows poor therapeutic effects, and combined treatment becomes a necessary option. YW002, a CpG ODN-containing sequence, has been proven to enhance antitumor effects in tumour-bearing mouse models. Moreover, as a broad-spectrum antimicrobial drug, nifuroxazide exhibited an anti-HCC effect through activation of p-Stat3. Here, we tested the effect of nifuroxazide on HCC in vitro and then explored the therapeutic effect of combined nifuroxazide and CpG ODN on HCC in vivo. Nifuroxazide inhibited proliferation, induced apoptosis and suppressed migration and invasion in HepG2 cells in vitro. The combination therapy using nifuroxazide and CpG ODN significantly suppressed the growth of tumours in tumour-bearing mice with few side effects and achieved better therapeutic effects on HCC than monotherapy. Moreover, combined nifuroxazide and CpG ODN therapy significantly induced apoptosis, enhanced the infiltration of CD4+ and CD8+ T lymphocytes and macrophages in tumour tissue, and increased the ratio of CD4+ and CD8+ T lymphocytes in the spleens of tumour-bearing mice. The introduction of this combination therapy combining nifuroxazide and CpG ODN provided a new strategy for HCC treatment.

Probing O-substituted nifuroxazide analogues against Leishmania: Synthesis, in vitro efficacy, and hit/lead identification.

Leishmaniasis is a neglected tropical disease affecting millions of people worldwide, with 650 000 to 1.1 million new infections reported annually by the World Health Organization. Current antileishmanial treatments are unsatisfactory due to the development of parasitic resistance and the toxicity associated with the drugs used, and this highlights the need for the development of new antileishmanial drugs. In this study, a series of nifuroxazide analogues were synthesized in a single step reaction and investigated for their antileishmanial potential. The sulfonate 1l, bearing pyridine ring, was deemed an antileishmanial hit, targeting the amastigotes of Leishmania (L.) donovani and L. major, the pathogens of visceral and cutaneous leishmaniasis, respectively, with micromolar potencies. The benzyl analogues 2c and 2d were also confirmed as submicromolar active leads against amastigotes of L. major. These analogues stand as promising candidates for further investigation involving the evaluation of their in vivo activities and molecular targets.

Detection of nitrofurans residues in honey using surface-enhanced Raman spectroscopy.

Residues of veterinary antibiotics in honey may be damaging to human health. Surface-enhanced Raman scattering spectroscopy (SERS) is an emerging technology widely applied in food safety. SERS has advantages of enabling fingerprint identification and fast detection, as well as does not require complex pretreatment. Considering the overuse of nitrofurans in honeybee breeding, SERS combined with spectral preprocessing was used to detect nitrofurantoin in honey. By using standardized experimental procedures and improved spectral correction methods, the lowest detection limit of nitrofurantoin was 0.1321 mg/kg. A good linear relationship in the partial least squares regression model was found among spiked samples, which allowed prediction of nitrofurantoin content in honey sample ( R C 2 $R_C^2$ = â€¯0.9744; R P 2 $R_P^2$ =  0.976; RMSECV = 1.0353 mg/kg; RMSEP  =  0.9987 mg/kg). Collectively, these results reliably demonstrated that quantification is more accurate when spectral preprocessing is better controlled. Therefore, this study indicates that SERS could be further implemented in fast and onsite detection of nitrofurantoin in honey for improved food safety. PRACTICAL APPLICATION: This article presents a novel SERS-based method for the rapid detection of nitrofurantoin residues in honey. The original spectra were corrected by multiple linear regression based on the fitting baseline. This study aims to develop a rapid onsite detection method for toxic hazardous substance residues in food.