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In order to understand the mechanism of bacterial drug resistance under the stress of quinolone antibiotics, this study took Aeromonas hydrophila as the research object, quantitative proteomics was used to compare the protein expression differences in A. hydrophila with and without enrofloxacin treatment. The results showed that total 446 differentially expressed proteins were identified by mass spectrometry, including 233 up-regulated proteins and 213 down-regulated proteins. Bioinformatics analysis showed that A. hydrophila survival may be promoted by up-regulating the expressions of most DNA repair and sulfur metabolism related proteins. Through the growth curve determination, cysteine combined with enrofloxacin can better inhibit the growth of bacteria. Meanwhile, qPCR was used to verify the expression levels of sulfur metabolism-related genes at the mRNA level, and it was uncovered that the differential expression levels of most genes at the transcription level were consistent with the protein level. These results indicate that sulfur metabolism plays an important role in the ENR stress of A. hydrophila. [ABSTRACT FROM AUTHOR]

Background: Terminalia ivorensis (TI) is used in West African ethnomedicine for the treatment of conditions including ulcers, malaria and wounds. Despite its widespread use, the phytochemical profile of TI remains largely undetermined. This research investigated the effects of extraction method, season, and storage conditions on the phytochemical composition of TI to contribute towards understanding the potential benefits. Methods: TI bark was collected in September 2014, September 2018 and February 2018 during the rainy or dry seasons in Eastern Region, Ghana. Samples were extracted sequentially with organic solvents (petroleum ether, chloroform, ethyl acetate and ethanol) or using water (traditional). Metabolites were identified by liquid chromatography–mass spectrometry/mass spectrometry and compared statistically by ANOVA. Results: A total of 82 different phytochemicals were identified across all samples. A greater yield of the major phytochemicals (44%, p < 0.05) was obtained by water as compared with organic extraction. There was also a higher concentration of metabolites present in cold (63%, p < 0.05) compared with hot water extraction. A significantly (p < 0.05) higher number of phytochemicals were identified from TI collected in the dry (85%) compared to the rainy season (69%). TI bark stored for four years retained 84% of the major phytochemicals. Conclusion: This work provides important information on composition and how this is modified by growing conditions, storage and method of extraction informing progress on the development of TI as a prophylactic formulation or medicine. [ABSTRACT FROM AUTHOR]

To evaluate the bioequivalence and safety of oral rivaroxaban tablets between a test formulation and a reference formulation in healthy Chinese subjects, a randomized, open, 2-formulation, 4-cycle, complete repeat crossover study was conducted under both fasting and fed states. Thirty-six healthy participants were enrolled separately for the fasting and fed groups, and each subject received a single oral dose of 20 mg of the test or reference formulation of rivaroxaban tablets per cycle. Blood samples were collected at specified intervals, and rivaroxaban was analyzed using liquid chromatography-tandem mass spectrometry. Under fasting and fed conditions, the 90% confidence intervals (CIs) for the geometric mean ratios of the maximum concentration (C max ), the area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC 0-t ), and the area under the curve extrapolated to infinity from time 0 (AUC 0-∞ ) all fell within the 80%-125% CI, and the upper limit of the 90% CIs for the test-to-reference ratio of the within-subject variability was <2.5. This indicated that the test formulation of rivaroxaban is bioequivalent to the reference formulation. Compared to the fasted state, the C max , AUC 0-t , and AUC 0-∞ of rivaroxaban increased significantly by factors of 2, 1.6, and 1.5, respectively, following oral administration of 20 mg of rivaroxaban in the fed state. This suggests that a high-fat diet significantly enhances the exposure to rivaroxaban. No serious adverse events were reported under fasting or fed conditions., (© 2025, The American College of Clinical Pharmacology.)

In this study, two hundred and thirteen liver samples were randomly collected from different ages and both sexes of cattle carcasses in El-Basatin abattoir, Cairo governorate, Egypt. One hundred ninety-seven samples out of the examined specimens were free from any bacterial infections; but showed enlargement and pallor. Thirty-nine specimens representing about 20% of the bacteria-free specimens were examined to detect the Aflatoxins and its metabolites using thin layer chromatography (TLC) and LC MS/MS. All Pathological appraisals were recorded and the genotoxicity of the studied mycotoxin was detected using single cell gel electrophoresis (Comet). Our study revealed that there were prominent deleterious effects of Aflatoxin M1 on the hepatic tissue. The detection of aflatoxins' metabolites in the hepatic tissues is of great importance on the health of human consuming organ meat; and on the other hand, it may affect the farm animals' performance. [ABSTRACT FROM AUTHOR]

• This is a sensitive method (1 ng/ml). • This method generates the shortest run time <1 min (rapid analysis). • This is the only published method that utilized Thiorphan_D7 as an internal standard. • There is an important application to prove the reliability of the new method, which is bioequivalence study in Jordanian subjects. Racecadotril, an anti-secretory medication, has been used as an adjuvant in an oral rehydration therapy for children experiencing severe diarrhea. Racecadotril is quickly converted to thiorphan, an active metabolite, after oral treatment, which mediates all subsequent activities. An efficient and rapid liquid chromatography-tandem mass spectrometry method was developed and fully validated to measure thiorphan in human plasma, using thiorphan-d7 as an internal standard. The extraction method used was protein precipitation while chromatographic separation was achieved using InertSil CN-3 (50 × 2.1 mm, 5 µm column). The assay was linear over the concentration range of 1–200 ng/ml with correlation coefficients of ≥0.9991. The intra- and inter-day precisions were less than 10.0 % for all concentrations investigated. 0.02 % aqueous formic acid and methanol (30:70 v: v) were used as mobile phases, with an analysis time of less than 1 min. This method proved stable under several conditions. The developed method worked well in a three-period pharmacokinetic bioequivalence study after a single oral administration of 100 mg racecadotril to 15 healthy Jordanian volunteers under fasting conditions. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is universal among patients with chronic liver disease. Vitamin D may be involved in the regulation of immune function of chronic hepatitis B and related to disease progression. Methods: The study was a cross-sectional study. The level of vitamin 25(OH)D was detected in patients with chronic hepatitis B, hepatitis B cirrhosis, hepatitis B cancer, and healthy groups by isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS). At the same time, the clinical data, biochemical indexes, and T lymphocyte subsets were collected to study the relationship between vitamin 25(OH)D deficiency and clinical indexes of hepatitis B patients. Results: The prevalence of vitamin D deficiency (< 20 ng/mL) was higher in patients with liver cancer group (96.97%, 10.59 ± 3.06 ng/mL) and cirrhosis group (93.18%, 11.85 ± 2.66 ng/mL) than in the healthy group (76.92%, 16.38 ± 5.53 ng/mL) and chronic hepatitis B group (77.83%, 15.06 ± 4.91 ng/mL). There were significant differences in vitamin 25(OH)D levels between the cirrhosis groups and the healthy groups, the liver cancer groups and the healthy groups, the hepatitis B cirrhosis groups and the chronic hepatitis B groups, the liver cancer groups and the chronic hepatitis B groups (p < 0.05). There was no significant difference in vitamin 25 (OH)D level between liver cancer group and hepatitis B cirrhosis group, healthy group and chronic hepatitis B group (p > 0.05). Vitamin 25(OH)D level was correlated with age (r = -0.24, p = 0.015), lymphocyte (r = 0.24, p = 0.015), hemoglobin (r = 0.28, p = 0.005), platelet (r = 0.27, p = 0.006), PTA (r = 0.33, p = 0.001), albumin (r = 0.30, p = 0.002), prealbumin (r = 0.39, p = 0.001), cholinesterase (r = 0.29, p = 0.003), CD3+ (r = 0.20, p = 0.04), CD3+ CD8+ (r = 0.20, p = 0.04), CD45+ (r = 0.24, p = 0.017), but none correlated with liver function and HBV-DNA. Conclusions: Vitamin D deficiency existed in patients with hepatitis B, which was related to the clinical progress of hepatitis B and may be involved in the regulation of immune function in patients with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Hypericum lanceolatum Lam. (H. lanceolatum) is a traditional medicinal plant from Reunion Island used for its pleiotropic effects mainly related to its antioxidant activity. The present work aimed to 1) determine the potential toxicity of the plant aqueous extract in vivo and 2) investigate its putative biological properties using several zebrafish models of oxidative stress, regeneration, estrogenicity, neurogenesis and metabolic disorders. First, we characterized the polyphenolic composition by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified chlorogenic acid isomers, quercetin and kaempferol derivatives as the major compounds. We then evaluated for the first time the toxicity of an aqueous extract of H. lanceolatum and determined a maximum non-toxic concentration (MNTC) in zebrafish eleutheroembryos from 0 to 96 hpf following OECD (Organization for Economic Cooperation and Development) guidelines. This MNTC test was also determined on hatched eleutheroembryos after 2 days of treatment (from 3 to 5 dpf). In our study, the anti-estrogenic effects of H. lanceolatum are supported by the data from the EASZY assay. In a tail amputation model, we showed that H. lanceolatum at its MNTC displays antioxidant properties, favors immune cell recruitment and tissue regeneration. Our results also highlighted its beneficial effects in metabolic disorders. Indeed, H. lanceolatum efficiently reduces lipid accumulation and body mass index in overfed larva- and adult-models, respectively. In addition, we show that H. lanceolatum did not improve fasting blood glucose levels in a hyperglycemic zebrafish model but surprisingly inhibited neurogenesis impairment observed in diabetic conditions. In conclusion, our study highlights the antioxidant, pro-regenerative, anti-lipid accumulation and pro-neurogenic effects of H. lanceolatum in vivo and supports the use of this traditional medicinal plant as a potential alternative in the prevention and/or treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Hypericum lanceolatum Lam. (H. lanceolatum) is a traditional medicinal plant from Reunion Island used for its pleiotropic effects mainly related to its antioxidant activity. The present work aimed to 1) determine the potential toxicity of the plant aqueous extract in vivo and 2) investigate its putative biological properties using several zebrafish models of oxidative stress, regeneration, estrogenicity, neurogenesis and metabolic disorders. First, we characterized the polyphenolic composition by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified chlorogenic acid isomers, quercetin and kaempferol derivatives as the major compounds. We then evaluated for the first time the toxicity of an aqueous extract of H. lanceolatum and determined a maximum non-toxic concentration (MNTC) in zebrafish eleutheroembryos from 0 to 96 hpf following OECD (Organization for Economic Cooperation and Development) guidelines. This MNTC test was also determined on hatched eleutheroembryos after 2 days of treatment (from 3 to 5 dpf). In our study, the anti-estrogenic effects of H. lanceolatum are supported by the data from the EASZY assay. In a tail amputation model, we showed that H. lanceolatum at its MNTC displays antioxidant properties, favors immune cell recruitment and tissue regeneration. Our results also highlighted its beneficial effects in metabolic disorders. Indeed, H. lanceolatum efficiently reduces lipid accumulation and body mass index in overfed larva- and adult-models, respectively. In addition, we show that H. lanceolatum did not improve fasting blood glucose levels in a hyperglycemic zebrafish model but surprisingly inhibited neurogenesis impairment observed in diabetic conditions. In conclusion, our study highlights the antioxidant, pro-regenerative, anti-lipid accumulation and pro-neurogenic effects of H. lanceolatum in vivo and supports the use of this traditional medicinal plant as a potential alternative in the prevention and/or treatment of metabolic disorders.

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDD measured ), and the dilation percentage of LVEDD from the norm (LVEDD acc. to HENRY ) were examined in combined and sex-specific regression models. To disclose protein-metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.

The Cys-loop pentameric ligand-gated ion channels comprise a dynamic group of proteins that have been extensively studied for decades, yielding a wealth of findings at both the structural and functional levels. The nicotinic acetylcholine receptor (nAChR) is no exception, as it is part of this large protein family involved in proper organismal function. Our efforts have successfully produced a highly pure nAChR in detergent complex (nAChR-DC), enabling more robust studies to be conducted on it, including beginning to experiment with high-throughput crystallization. Our homogeneous product has been identified and extensively characterized with 100% identity using Nano Lc MS/MS and MALDI ToF/ToF for each nAChR subunit. Additionally, the N-linked glycans in the Torpedo californica-nAChR (Tc-nAChR) subunits have been identified. To study this, the Tc-nAChR subunits were digested with PNGase F and the released glycans were analyzed by MALDI-ToF. The MS results showed the presence of high-mannose N-glycan in all native Tc-nAChR subunits. Specifically, the oligommanose population Man8-9GlcNac2 with peaks at m/z 1742 and 1904 ([M + Na]+ ions) were observed., (© 2023 The Authors. PROTEOMICS published by Wiley-VCH GmbH.)

The intense use of pesticides against plant pests and diseases during cucumber growing in greenhouses may lead to high levels of pesticide residues in the final product. The concentration of pesticide residues in cucumber fruits can change during subsequent pickle processing steps and could be affected with washing, sterilising or keeping at low pH levels during fermentation1. This study was conducted to detect the residue levels of 2 acaricides, 3 insecticides and 6 fungicides in cucumbers grown at greenhouse during each step of pickling processing (washing, fermentation and pasteurisation). Pesticides were applied at their recommended field doses with a knapsack sprayer under greenhouse conditions on three independent plots 3 days before harvesting (Preharvest interval-PHI). After harvesting, raw materials were processed with two different processing techniques (canned and fermented) according to Compendium of Representative Processing Techniques Investigated in Regulatory Studies for Pesticides2. The extraction and cleaning up of the pesticides, namely, acetamiprid, ametoctradin, azoxystrobin, chlorantraniliprole, deltamethrin, difenoconazole, dimethomorph, etoxazole, fluopicolide, propamocarb and spiromesifen, were conducted by using QuEChERS method3. The residue levels were detected with LC MS/MS. The multi-residue analysis method was validated according to the SANTE guidelines4,5. The processing factor (pf) values obtained during canned pickle processing steps such as washing, pasteurisation and storage (21 days), were found as 0.25-1.10; 0.03-0.89; 0.01-0.68, respectively. The pf values of fermented pickle processing steps like washing, fermentation and pasteurisation, ranged with 0.39-0.98; 0.03-0.79; 0.01-0.85, respectively. During both types of pickle processes, pesticide residues remained lower than the Maximum Residue Levels. This study was funded by the collaboration of Bursa Uludag University and Perla Fruit Company with the grant number FKA-2021-531. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is a widespread opportunistic pathogen of aquatic fishes in freshwater habitats. The current emergence of antimicrobial-resistant A. hydrophila has been reported in the world while the bacterial antibiotics adaptive mechanism remains poorly explored. In this study, using quantitative proteomics technology, the behavior of A. hydrophila was investigated by comparing the differentially expression proteins between with and without kanamycin (KAN) treatment. A total of 374 altered proteins including 184 increasing and 190 proteins decreasing abundances were quantified when responding to KAN stress. The bioinformatics analysis showed that stress related proteins were hub proteins that significantly increased to reduce the pressure from the misreading of mRNA caused by KAN. Moreover, several metallic pathways, such as oxidative phosphorylation and TCA cycle pathways may affect KAN resistance. Finally, eight selected genes were deleted and their antibiotics susceptibilities to kanamycin were valued, respectively. Results showed that OmpA II family protein A0KI26, and two-component system protein AtoC may involve in the KAN resistance in this study. In general, our results provide an insight into the behaviors of bacterial responding to KAN stress, and demonstrate the intrinsic antibiotics adaptive mechanism of A. hydrophila. In this study, the differentially expressed proteins (DEPs) of A. hydrophila strain between with and without kanamycin (KAN) were compared by using a data-independent acquisition (DIA) - based quantitative proteomics method. Bioinformatics analysis showed that stress - related proteins are hub proteins that significantly increased under KAN stress. Moreover, several metallic pathways, such as oxidative phosphorylation and citrate cycle (TCA cycle) pathways, can affect KAN resistance. Finally, our antibiotics susceptibility assay showed that the protein A0KI26 of the OmpA II family, and the AtoC of the two-component system may involve in KAN resistance in this study. These results provide insights into the antibiotics adaptation mechanism of A. hydrophila when responding to KAN stress. [Display omitted] • A total of 374 DEPs were detected under the stress of KAN. • Stress-related proteins increased significantly in the presence of kanamycin. • A0KI26 and AtoC may involve in the KAN resistance. [ABSTRACT FROM AUTHOR]