Concentrations Of Doxycycline Research Articles

Doxycycline-Mediated Inhibition of Snake Venom Phospholipase and Metalloproteinase.

Warfighters are exposed to life-threatening injuries daily and according to the Joint Trauma System Military Clinical Practice Guideline-Global Snake Envenomation Management snakebites are a concerning threat in all theaters of operation. Snake venom is a complex mixture of toxins including phospholipases A2 (PLA2) and snake venom metalloproteinases (SVMP) that produce myotoxic, hemotoxic, and cytotoxic injuries. Antibody-based antivenom is the standard of care but new approaches including small-molecule inhibitors have gained attention in recent years. Doxycycline is an effective inhibitor of human metalloproteinases and PLA2. The enzymatic activities of 3 phylogenetically distinct snakes: Agkistrodon piscivorus, Naja kaouthia, and Daboia russelii were tested under inhibitory conditions using doxycycline. Enzymatic activity of PLA2 and SVMP was measured in N. kaouthia, D. russelii, and A. piscivorus venom alone and with doxycycline using EnzChek Phospholipase A2 and Gelatinase Assay Kits. A 1-way ANOVA with Tukey's post-hoc test was used to conduct comparative analysis. The median lethal dose of the venoms, the effective dose of doxycycline, and creatine kinase (CK) inhibition levels were measured in a murine model with adult Bagg Albino (BALB/c) mice using intramuscular injections. Median lethal and effective doses were determined using Spearman-Karber's method and a 1-way ANOVA with Tukey's post-hoc test was used to compare CK inhibition levels. Phospholipases A2 activity was reduced to 1.5% to 44.0% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline when compared to venom-only controls (P < .0001) (Fig.1A). Snake venom metalloproteinases activity was reduced to 4% to 62% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline (P < .0001) (Fig.1B). The lethal dose (LD50) values of the venoms in the murine model were calculated as follows: A. piscivorus = 20.29 mg/kg (Fig.2A), N. kaouthia = 0.38 mg/kg (Fig.2B), and D. russelii = 7.92 mg/kg (Fig.2C). The effective dose (ED50) of doxycycline in A. piscivorus was calculated to be 20.82 mg/kg and 72.07 mg/kg when treating D. russelii venom. No ED50 could be calculated when treating N. kaouthia venom (Fig.3). Creatine kinase activity was significantly decreased in all 3 venoms treated with doxycycline (P < .0001) (Fig.4). Doxycycline reduced PLA2- and SVMP-related lethality, particularly in A. piscivorus envenomings and in a limited capacity with D. russelii revealing its promise as a treatment for snakebites. In addition, CK activity, a common indicator of muscle damage was inhibited in mice that received doxycycline-treated venom. The doxycycline concentrations identified in the ED50 studies correspond to 1,456 to 5,061 mg dosages for a 70 kg human. Factors including venom yield and snake species would affect the actual dosage needed. Studies into high-dose doxycycline safety and its effectiveness against several snake species is needed to fully translate its use into humans. Based on this work, doxycycline could be used as a treatment en route to higher echelons of care, providing protection from muscle damage and reducing lethality in different snake species.

High-efficiency ternary CeO2/WO3/AC photocatalyst supported by biomass waste-derived activated carbon for efficient doxycycline photodegradation: Optimization of synthesis conditions and operational parameters

Herein, a stable and reusable photocatalyst based on activated carbon (AC) with varying CeO2/WO3 loadings is synthesized and optimized using Central Composite Design (CCD) with the intention of Doxycycline (DOX) degrading as an organic pollutant. Prepared optimum photocatalyst have been characterized through XRD, BET, FE-SEM, EDS-Mapping, TEM, FT-IR, and UV–Vis band gap analyses. Additionally, the effect of operational parameters including catalyst dosage (0.2–1.4 g.L−1), DOX concentration (10–50 ppm), irradiation time (20–140 min), and pH (2–10) on DOX degradation is investigated by CCD in order to highly-efficient DOX degradation. The best working condition shows an experimental degradation efficiency of 97.23%. Moreover, selected CeO2/WO3/AC photocatalyst remove 83.11% of COD from DOX solution. The h+ and •O2− radicals are found to be essential for the destruction of the DOX due to heir strong and nonselective oxidation characteristics. Furthermore, the stability of the selected photocatalyst observed after undergoing five degradation cycles.

Chlorogenic acid attenuates tet (X)-mediated doxycycline resistance of Riemerella anatipestifer.

The increasing resistance of R. anatipestifer has posed a significant threat to the poultry industry in recent years. The tet gene is the primary determinant of tetracycline resistance in numerous bacteria, and the enzyme modification gene tet(X) is predominantly detected in tetracycline-resistant R. anatipestifer strains. In this study, we evaluated the susceptibility of both the standard strain and clinical isolates of R. anatipestifer to doxycycline. And the expression levels of tet(X), tet(A), and tet(O) genes were detected. To assess drug susceptibility, shuttle plasmids were constructed to transfer the tet(X) gene into the standard strain of R. anatipestifer followed by treatment with chlorogenic acid. The results revealed that the minimum inhibitory concentration of doxycycline for the standard strain was 0.25μg/mL, whereas it exceeded 8μg/mL for the clinical isolates. Furthermore, there was a significant upregulation observed in expression levels of tet(X), tet(A), and tet(O) genes among induced strains. Interestingly, when transferring the tet(X) gene into the standard strain, its sensitivity to doxycycline decreased; however, MIC values for chlorogenic acid remained consistent between both standard and drug-resistant strains of R. anatipestifer. Moreover, we made a surprising discovery that screening passage with chlorogenic acid resulted in increased sensitivity of R. anatipestifer to doxycycline. Further analysis demonstrated a reversal in expression trends among three differentially expressed genes within induced drug resistance group after intervention with chlorogenic acid. The main objective behind this study is to investigate both killing effect exerted by chlorogenic acid on drug-resistant R. anatipestifer as well as its regulatory impact on drug resistance genes. This will provide novel insights and theoretical basis towards development of chlorogenic acid as a promising drug for treatment and control of drug resistance in R. anatipestifer.

Engineered design of MnFe2O4/CoNiFe-LTH/g-C3N4 heterocatalyst for doxycycline degradation via Fenton oxidation process: Optimization and mechanism

The removal of organic contaminants from waterways is vital to the ecosystem. A novel MnFe2O4/CoNiFe-LTH/g-C3N4 catalyst was synthesized via self-assembly preparation and linked with H2O2 for the Fenton degradation of doxycycline (DXY). The MnFe2O4/CoNiFe-LTH/g-C3N4 was characterized using FTIR, XRD, XPS, VSM, SEM, GC-MS, and ICP-OES. Interestingly, the magnetically separable and high-stability catalyst achieved 89.11% DXY degradation, and 69.30% TOC removal efficiency within 60 and 120 min, respectively (at pH = 7.5, catalyst dosage= 0.01g, H2O2 = 400 ppm, T= 20 °C, and DXY concentration= 100 ppm). In addition, the synergistic effect of metal cations (Co, Ni, Fe, and Mn) triggered Fenton degradation through a continuous closed cycle of electrons. A pseudo-first-order kinetic model also fitted DXY degradation with MnFe2O4/CoNiFe-LTH/g-C3N4. Furthermore, the radical pathway mechanism was confirmed with XPS before and after degradation and with radical scavenging tests. The DXY degradation pathway was speculated by GC-MS analysis. Quantitative structure-activity relationship (QSAR) was applied to assess intermediates for developmental toxicity. The MnFe2O4/CoNiFe-LTH/g-C3N4 catalytic activity on H2O2 decomposition was determined via titrimetric analysis. Recycling tests and ICP-OES measurements were further used to investigate the catalyst's resilience and reusability. Besides, MnFe2O4/CoNiFe-LTH/g-C3N4 demonstrated a performance of 70% over eight catalytic degradation runs with minimal metal leaching. Eventually, MnFe2O4/CoNiFe-LTH/g-C3N4 is a viable catalyst for breaking down organic contaminants in wastewater.

Serine deamination by human serine racemase synergizes with antibiotics to curtail the replication of Chlamydia trachomatis

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. In view of this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates the anti-chlamydial effect of elevated serine concentrations. In addition to reversibly converting l-serine to d-serine, serine racemase also deaminates serine via β-elimination. We have determined that d-serine does not directly impact Chlamydia; rather, ammonia generated by serine deamination limits the productive chlamydial replication. Our findings imply that ammonia produced within host cells can traverse the chlamydial inclusion membrane. Further, this property of serine deaminase can be exploited to sensitize Chlamydia to concentrations of doxycycline that are otherwise not bactericidal. Because exogenously elevated levels of serine can be tolerated over extended periods, the broad expression pattern of serine racemase indicate it to be a host enzyme whose activity can be directed against multiple intracellular bacterial pathogens. From a therapeutic perspective, by demonstrating host metabolism can be skewed to generate an anti-bacterial metabolite that synergizes with antibiotics, we believe our results provide a new approach to target intracellular pathogens.

Adsorption–photocatalysis synergy of reusable mesoporous TiO2–ZnO for photocatalytic degradation of doxycycline antibiotic

The potentials of mesoporous TiO2–ZnO (3TiZn) were explored on photocatalytic degradation of doxycycline (DOX) antibiotic, likewise the influence of adsorption on the photocatalytic process. The 3TiZn was characterized for physical and chemical properties. Stability, reusability, kinetic and the ability of 3TiZn to degrade high concentration of pollutant under different operating conditions were investigated. Photocatalytic degradation of DOX was conducted at varied operating conditions, and the best was obtained at 1 g/L catalyst dosage, solution inherent pH (4.4) and 50 ppm of DOX. Complete degradation of 50 ppm and 100 ppm of DOX were attained within 30 and 100 min of the reaction time, respectively. The stability and reusability study of the photocatalyst proved that at the tenth (10th) cycle, the 3TiZn is as effective in the degradation of DOX as in the first cycle. This may be attributed to the fusion of the mixed oxides during calcination. The 3TiZn is mesoporous with a pore diameter of 17 nm, and this boosts it potential to degrade high concentration of DOX. It was observed that the adsorption capacity of 3TiZn enhance the photocatalytic process. It can be emphasized that 3TiZn portrayed a remarkable catalyst stability and good potentials for industrial application.

Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 μM), ML-7 (0.5 μM), and L-NAME (2 μM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.

Abstract 2111: Impact of HER2 Expression on trastuzumab deruxtecan(T-DXd) efficacy

Abstract Background: T-DXd is an FDA-approved anti-HER2 Antibody Drug Conjugate (ADC), which has shown clinical efficacy in breast cancers with either overexpression or low-level expression of HER2. The benefit of T-DXd across the spectrum of HER2 expression has called into question the relevance of HER2 expression level as relevant parameter for T-DXd sensitivity. We sought to experimentally address the relevance of HER2 expression level upon the degree of T-DXd response. Methods: A series of isogenic models was generated that expressed different levels of surface HER2 using a doxycycline-inducible promoter. These were analyzed for impact of differential expression level upon T-DXd internalization and drug response. Human breast cancer samples were analyzed for HER2 expression levels and association with clinical response to T-DXd under an IRB approved protocol. Results: Induction of different levels of HER2 at specified doxycycline concentrations was verified in multiple models using immunoblotting and FACS. These different levels appeared to correspond to clinical breast cancer immunohistochemistry (IHC) scoring levels to 0, 1+, 2+, and 3+. The models were analyzed for T-DXd response and showed increasing levels of HER2 led to increase lysosomal uptake of T-DXd (p&amp;lt;0.0001). Moreover, elevation of HER2 levels led to lower concentrations of T-DXd needed to suppress tumor growth. Analyses of the effects of increasing levels of HER2 upon xenograft response to T-DXd are ongoing. Finally, retrospective analyses of a cohort of 50 breast cancer patients treated with T-DXd revealed that higher levels of HER2 corresponded to longer time on treatment (time to progression). Conclusion: We observe a consistent relationship between elevated expression of HER2 and breast cancer response to T-DXd. The findings highlight the relevance of HER2 expression level as a biomarker of T-DXd response and support the potential value of therapeutic strategies that can induce HER2 surface expression levels to enhance response. Citation Format: Wanyi Chen, Joshua Drago, Avantika Gupta, Bo Liu, Sarat Chandarlapaty. Impact of HER2 Expression on trastuzumab deruxtecan(T-DXd) efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2111.

Abstract 472: Long non-coding RNA MIR31HG-derived circRNA enhances the oncogenicity of oral carcinoma

Abstract Introduction: Oral carcinoma (OC) represents a significant health challenge, with the role of non-coding RNAs, particularly microRNAs and long non-coding RNAs (LncRNAs), being well-established in its progression. However, the implications of circular RNAs (circRNAs) in this context are less well understood, presenting a notable gap in current research. Our study focuses on the MIR31HG LncRNA, identified as crucial in OC, particularly its role in producing circRNA, as evidenced by sequencing. This specific MIR31HG-derived circRNA, designated 31HGcircR, which contains a potential open reading frame (ORF), and may demonstrate phenotypic significances. Alterations to 31HGcircR, either through knockout or ORF mutation, result in remarkable phenotypic changes, highlighting its potential importance in the pathogenesis of OC. Methods: We implemented 31HGcircR overexpression in OC cell lines, utilizing the TetOff system for gene expression control. CRISPR/Cas9 was employed for gene knockout, and siRNA for gene knockdown. Gene expression was quantified using qPCR. Additionally, the BaseScope assay was used to label and detect the spatial expression of overexpressed 31HGcircR within the cells. Assays to assess cell proliferation, invasion, migration, anchorage-independent growth (AIG), and clonogenicity were conducted. Results: The findings revealed specific junctions of 31HGcircR and varied expression levels across different OC cell lines. There was a significant correlation among the expression of 31HGcircR, MIR31HG and miR-31-5p. Notably, the knockdown of 31HGcircR led to pronounced inhibition of cell growth, migration, invasion, AIG, and clonogenic activity. Conversely, overexpression of 31HGcircR or its ORFs augmented invasion and clonogenic potential in certain cell lines. The TetOff system demonstrated that minimal concentrations of Doxycycline effectively suppressed 31HGcircR expression, with reversible effects upon removal. Knocking out 31HGcircR resulted in reduced invasion and clonogenic capabilities. Conclusion: This study provides clues demonstrating the oncogenic roles of 31HGcircR in OC, which simulate the functions of MIR31HG or miR-31-5p. The changes in cell phenotypes following 31HGcircR manipulation suggest its potential as a therapeutic target or biomarker in OC. These findings offer valuable insights, contributing to the evolving understanding of circRNAs in cancer research and potential treatment avenues. Citation Format: Chung-Hsien Chou, Hsi-Feng Tu, Kuo-Wei Chang, Shu-Chun Lin. Long non-coding RNA MIR31HG-derived circRNA enhances the oncogenicity of oral carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 472.

Elucidating doxycycline biotransformation mechanism by Chryseobacterium sp. WX1: Multi-omics insights

Doxycycline (DOX) represents a second-generation tetracycline antibiotic that persists as a challenging-to-degrade contaminant in environmental compartments. Despite its ubiquity, scant literature exists on bacteria proficient in DOX degradation. This study marked a substantial advancement in this field by isolating Chryseobacterium sp. WX1 from an activated sludge enrichment culture, showcasing its unprecedented ability to completely degrade 50 mg/L of DOX within 44 h. Throughout the degradation process, seven biotransformation products were identified, revealing a complex pathway that began with the hydroxylation of DOX, followed by a series of transformations. Employing an integrated multi-omics approach alongside in vitro heterologous expression assays, our study distinctly identified the tetX gene as a critical facilitator of DOX hydroxylation. Proteomic analyses further pinpointed the enzymes postulated to mediate the downstream modifications of DOX hydroxylation derivatives. The elucidated degradation pathway encompassed several key biological processes, such as the microbial transmembrane transport of DOX and its intermediates, the orchestration of enzyme synthesis for transformation, energy metabolism, and other gene-regulated biological directives. This study provides the first insight into the adaptive biotransformation strategies of Chryseobacterium under DOX-induced stress, highlighting the potential applications of this strain to augment DOX removal in wastewater treatment systems containing high concentrations of DOX.

Pharmacokinetics of single dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections

Clinical trials showed a single oral dose of doxycycline taken after sex protects against STIs among men who have sex with men (MSM) but not women. Pharmacokinetic data at vaginal, rectal and penile sites of STI exposure are lacking. We examined vaginal, rectal and urethral doxycycline concentrations in men and women to better inform STI prevention. Doxycycline pharmacokinetics in male and female participants 18-59 years of age were evaluated in blood and urine and on rectal and vaginal swabs collected at 1, 2, 4, 8, 24, 48, 72, 96 and 168h after receiving a 200mg oral doxycycline dose in a non-randomised single dose open label single centre study in Atlanta, Georgia. Rectal, vaginal, and cervical biopsies and male urethral swabs were collected 24h after dosing (Trial registration: NCT04860505). Doxycycline was measured by liquid chromatography-mass spectrometry. Eleven male and nine female participants participated in the study. Doxycycline concentrations on rectal and vaginal swabs collected up to 96h after dosing were approximately twice those of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and tetracycline-sensitive Neisseria gonorrhoeae, respectively. Geometric mean doxycycline concentrations in male urethral secretions (1.166μg/mL; 95% CI 0.568-2.394μg/mL), male rectal (0.596μg/g; 0.442-0.803μg/g), vaginal (0.261μg/g; 0.098-0.696μg/g) and cervical tissue (0.410μg/g; 0.193-0.870μg/g) in biopsies collected 24h after dosing exceeded MICs. Plasma and urine doxycycline levels defined adherence markers up to four and seven days postdosing, respectively. No adverse events were reported in this study. Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline. Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).

Impact of Doxycycline Addition on Activated Sludge Microflora and Microbial Communities

Municipal wastewater treatment plants (WWTPs) are exposed to high concentrations of micropollutants that can impact conventional activated sludge treatment. The consequences of this include failure to meet discharge standards and the disintegration of flocs, leading to poor sludge settleability. This lab-scale study focuses on the influence of doxycycline, an antibiotic widely used against human and animal diseases, on protozoa, metazoa, and bacterial communities under sludge growing conditions. Doxycycline was added to the mixed liquor of a communal WWTP up to 0, 100, 200, and 400 mg of doxycycline L−1 and incubated in batch conditions for 23 days. The regular addition of nutrient and carbon sources was preformed every 2 days to prevent sludge starvation. Sludge growth, conductivity, and settleability were measured and compared to sludge microbial community structure, determined by microscopic observations and high-throughput 16S rDNA sequencing. The high doxycycline concentration negatively impacted settleability and correlated with a decrease in bacterial diversity and floc disintegration. The addition of doxycycline promoted the enrichment of Proteobacteria Brevundimonas sp., Luteibacter anthropi, and the Bacteroidetes Chryseobacterium massoliae. These species are known to be resistant to a wide spectrum of antibiotics, including tetracyclines. A study of a larger scale may be conducted based on this study’ results.

Effects of two pharmaceuticals: Doxycycline and norfloxacin on plant and animal organisms living in the freshwater

The main reason for the appearance of pharmaceutical compounds in the aquatic environment is their regular excretion by humans and animals in an unchanged form or slightly metabolized. Pharmaceuticals limit the habitable living environment for aquatic organisms, because they can be toxic not only to bacteria but also to non-target organisms. Plants of the Lemnoideae subfamily and crustaceans Daphniindae family are widely used as bioindicators in freshwater environmental risk assessments. This study aimed to use biotests (Lemna test and Daphtoxkit) to determine the effect of two pharmaceuticals: antibiotic – Doxycycline (DOX) and semi-synthetic chemotherapeutic drug – Norfloxacin (NOR) on plants Lemna minor and crustaceans Daphnia magna. Standard Lemna test was extended to include pharmaceutical effects on plant chlorophyll content (LCC) and fluorescence (Fo, Fm, and Fv/Fm), and the confirmation of drug toxicity was the biotest Daphtoxkit assessing the immobilization (IM) of organisms. Studies have shown that DOX was more toxic than NOR on tested aquatic organisms: plants and crustaceans. The lowest observed effect concentration (EC20) of DOX and NOR reduced by 20 % LCC and Iy of L. minor was 2.14 and 8.11 mg × L−1, respectively. The LCC was an early and sensitive indicator of the phytotoxic effects of DOX in L. minor before morphological changes were observed. Confirmation of drug toxicity was the Daphtoxkit. The EC20 (180. min) of DOX and NOR, IM of daphnia by 20 % was 117.18 and 215.42 mg × L−1, respectively. In conclusion, DOX and NOR in aquatic environments may have significant implications for tested organisms and their ecosystems.

Pentachlorophenol affects doxycycline and tetracycline resistance genes in soil by altering microbial structure

Tetracycline antibiotics play a vital role in animal husbandry, primarily employed to uphold the health of livestock and poultry. Consequently, when manure is reintegrated into farmland, tetracycline antibiotics can persist in the soil. Simultaneously, to ensure optimal crop production, organochlorine pesticides (OCPs) are frequently applied to farmland. The coexistence of tetracycline antibiotics and OCPs in soil may lead to an increased risk of transmission of tetracycline resistance genes (TRGs). Nevertheless, the precise mechanism underlying the effects of OCPs on tetracycline antibiotics and TRGs remains elusive. In this study, we aimed to investigate the effects of OCPs on soil tetracycline antibiotics and TRGs using different concentrations of doxycycline (DOX) and pentachlorophenol (PCP). The findings indicate that PCP and DOX mutually impede their degradation in soil. Furthermore, our investigation identifies Sphingomonas and Bacillus as potential pivotal microorganisms influencing the reciprocal inhibition of PCP and DOX. Additionally, it is observed that the concurrent presence of PCP and DOX could impede each other's degradation by elevating soil conductivity. Furthermore, we observed that a high concentration of PCP (10.7 mg/kg) reduced the content of efflux pump tetA, ribosome protective protein tetM, tetQ, and passivating enzyme tetX. In contrast, a low PCP concentration (6.4 mg/kg) only reduced the content of ribosome protective protein tetQ. This suggests that PCP may reduce the relative abundance of TRGs by altering the soil microbial community structure and inhibiting the potential host bacteria of TRGs. These findings have significant implications in understanding the combined pollution of veterinary antibiotics and OCPs. By shedding light on the interactions between these compounds and their impact on microbial communities, this study provides a theoretical basis for developing strategies to manage and mitigate their environmental impact, and may give some information regarding the sustainable use of antibiotics and pesticides to ensure the long-term health and productivity of agricultural systems.

Histidine-capped copper nanoclusters for in situ amplified fluorescence monitoring of doxycycline through inner filter effect.

There is a significant need to accurately measure doxycycline concentrations in view of the adverse effects of an overdose on human health. A fluorescence (FL) detection method was adopted and copper nanoclusters (CuNCs) were synthesized using chemical reduction technology. Based on FL quenching with doxycycline, the prepared CuNCs were used to explore a fluorescent nanoprobe for doxycycline detection. In an optimal sensing environment, this FL nanosensor was sensitive and selective in doxycycline sensing and displayed a linear relationship in the range 0.5-200 μM with a detection limit of 0.092 μΜ. A characterization test demonstrated that CuNCs offered active functional groups for identifying doxycycline using electrostatic interaction and hydrogen bonds. Static quenching and the inner filter effect (IFE) resulted in weakness in the FL of His@CuNCs with doxycycline with great efficiency. This suggested nanosensor was revealed to be a functional model for simple and rapid detection of doxycycline in real samples with very pleasing accuracy.

The effect of doxycycline on canine neutrophil functions

Doxycycline is a broad-spectrum tetracycline-class antibiotic that is frequently used to treat bacterial infections. Its use has also been described in immune-mediated diseases due to its immunomodulatory properties. The aim of this study was to evaluate the immunomodulatory effect of doxycycline on canine neutrophil functions. Therefore, the release of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) were determined after incubation of canine PMNs with doxycycline in three different concentrations (4 µg/mL, 20 µg/mL and 200 µg/mL) for one and three hours, respectively. Additionally, a neutrophil killing assay with a doxycycline-resistant Staphylococcus aureus was performed to determine the bactericidal effect of doxycycline treated PMNs in presence of plasma. Doxycycline significantly diminished the production of ROS. However, doxycycline concentrations of 4 µg/mL and 20 µg/mL significantly induced NETs. A synergistic bacteriostatic effect of PMNs and doxycycline on a doxycycline-resistant Staphylococcus aureus isolate was detectable. However, already PMNs and especially doxycycline alone inhibited the growth. In summary, doxycycline showed a concentration-dependent immunomodulatory property in canine PMNs with a reduced ROS production and increased NET-induction. This immunomodulatory effect resulted in a slightly increased elimination of a doxycycline-resistant Staphylococcus aureus by the doxycycline plasma concentrations achieved in dogs.

Dandelion-like Cu-Ni LDH-decorated biochar/aminated chitosan composite for boosting Fenton-like degradation of doxycycline: Insights into performance and mechanism

This study fabricated a novel biochar/amine chitosan composite (BC/AmCS) decorated with dandelion-like Copper-Nickel layered double hydroxide (Cu-Ni LDH) for Fenton-like degradation of doxycycline (DOX). The Fenton-like degradation of DOX proceeded at varied experimental conditions, implying the superior degradation efficacy of Cu-Ni LDH/BC/AmCS composite at pH = 8, H2O2 = 400 mg/L, and composite dosage = 0.03 g/L. Interestingly, results showed that the Fenton-like degradation % of DOX reached 86.9 % after 1 h at a high concentration of DOX (500 mg/L). Furthermore, it was recorded a synergistic effect between adsorption, and Fenton-like processes during the degradation of DOX, where the adsorption % attained 46.9 %. Moreover, kinetic modeling clarified the fitting of a pseudo-first-order kinetic model to model the degradation of DOX by Cu-Ni LDH/BC/AmCS/H2O2 system. Based on the X-ray photoelectron spectroscopy (XPS), and quenching test, the Fenton-like degradation mechanism of DOX followed a radical pathway forming a continuous redox cycle in Cu-Ni LDH/BC/AmCS. In addition, the degradation pathway was presumed via gas chromatography–mass spectrometry (GC–MS) measurements. The developmental toxicity of the produced intermediates was assessed using quantitative structure–activity relationship (QSAR) prediction. The durability of Cu-Ni LDH/BC/AmCS catalyst was scrutinized by performing a cycling test for 5 runs, and measuring the metal leaching. The H2O2 decomposition was determined via the potassium titanium (IV) oxalate spectrophotometric technique. Eventually, Cu-Ni LDH/BC/AmCS composite could be recommended as a promising catalyst for the efficient degradation of organic pollutants from wastewater.

Smartphone-assisted colorimetric dual-mode sensing system based on europium-doped metal–organic frameworks for rapid on-site visual detection of Fe3+ and doxycycline

Exploring a rapid, sensitive, low-cost, in-situ intelligent monitoring multi-target fluorescence detection platform is important for food safety and environmental monitoring. A dual-mode ratiometric fluorescence sensing system integrated with a smartphone based on a luminescent metal–organic framework (NH2-MIL-53) and CdTe/Eu was developed for visual, in-situ analysis of Fe3+ and doxycycline (DOX) in this paper. Interestingly, with increasing Fe3+ concentration, the fluorescence sensing system exhibits dual-emission with CdTe QDs at 540 nM as the response signal and NH2-MIL-53 at 438 nm as the reference signal, resulting in a significant color shift of fluorescence color from blue-green to blue, with a linear range of 5––1550 nM and a detection limit of 1.08 nM. In the presence of DOX, the blue fluorescence of NH2-MIL-53 and the green fluorescence of CdTe QDs were quenched respectively by the internal filtering effect and the photoelectron transfer effect. While DOX enhances the red fluorescence of Eu3+ by the antenna effect, forming a triple-emission fluorescence sensor. The visual color of this fluorescent sensor shifted from blue green to grey to pink-white to pink to fuchsia to red as the DOX concentration increased with a detection limit of 0.11 nM. Furthermore, the developed intelligent sensing platform achieved real-time in-situ detection of Fe3+ and DOX with detection limit of 1.47 nM and 6.43 nM, respectively. The platform was applied to detection actual samples with satisfactory results, which proved a promising application for real-time on-site food safety monitoring and human health monitoring.

Preliminary study of doxycycline adsorption from aqueous solution on alkaline modified biochar derived from banana peel

This study explores the adsorption of doxycycline (DOX) from aqueous solutions onto biochar derived from banana peel, which was prepared using a potassium hydroxide activation method (KOH-BPB). The biochar properties were characterized based on morphology, surface area (SBET of 710.241 m&lt;sup&gt;2&lt;/sup&gt; g&lt;sup&gt;-1&lt;/sup&gt;), functional groups, and surface charge (pHPZC = 7.7). Parameters, including initial pH, DOX concentration, and ionic strength, that influenced the DOX adsorption capacity of KOH-BPB were examined. Adsorption equilibrium of DOX on KOH-BPB was assessed through four isothermal models: the Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich models. The obtained data were most compatible with the Langmuir model (R&lt;sup&gt;2&lt;/sup&gt; = 0.9879). KOH-BPB has a maximum DOX absorption capacity of 121.95 mg g&lt;sup&gt;-1&lt;/sup&gt; which exceeds that of many comparable absorbents. The maximum DOX removal was 96.7% at pH 6, a DOX concentration of 20 mg L&lt;sup&gt;-1&lt;/sup&gt;, and a KOH-BPB dose of 1.0 g L&lt;sup&gt;-1&lt;/sup&gt;. These findings reveal that biochar from banana peel effectively removes antibiotic residues from water. This study provides a potential, low-cost, and environmentally friendly adsorbent.

Impact of azithromycin, doxycycline and redox-active small molecules on amoxicillin-induced Chlamydia pneumoniae persistence

Amoxicillin is recommended as primary treatment for community-acquired bacterial pneumonia (CABP). 5–10% of CABP cases are caused by Chlamydia pneumoniae, an obligate intracellular bacterium which responds to beta-lactam antibiotics by converting to a persistent phenotype. To support rational pharmacotherapy of C. pneumoniae infections, we investigated how clinically relevant concentrations of azithromycin and doxycycline affect amoxicillin induced C. pneumoniae persistence. Given the known role of redox state alterations in the action of bactericidal antibiotics and widespread use of redox-active dietary supplements when experiencing respiratory symptoms, we also studied how redox active compounds affect the studied antibiotic treatments. Our data demonstrate that clinically applied amoxicillin concentrations (10 and 25 mg/l) fail to eradicate C. pneumoniae infection in respiratory epithelial cells. Transmission electron microscopy (TEM) of amoxicillin-treated C. pneumoniae infected cells reveal aberrant bacterial morphology characteristic of chlamydial stress response. Amoxicillin was also found to significantly limit the antichlamydial effect of azithromycin or doxycycline. However, based on quantitative culture and quantitative PCR data, azithromycin was superior to doxycycline in C. pneumoniae eradication either as monotherapy or in combination with amoxicillin. Amoxicillin was also found to decrease respiratory epithelial cell glutathione (GSH) levels, whereas redox-active dibenzocyclooctadiene lignans increased C. pneumoniae load in amoxicillin-treated cultures up to two-fold. These data highlight the impact of relative administration time on the efficacy of antichlamydial antibiotics and indicate unfavorable interactions between amoxicillin and redox-active small molecules.