UNASSIGNED: This study was conducted to compare the effects of nisin (NIS) and ionophore antibiotic monensin (MON) on the growth performance, rumen fermentation, nutrient digestion and plasma metabolites of fattening Hu sheep.
UNASSIGNED: Thirty-six male Hu sheep (23.5 ± 1.0 kg) were divided into two blocks based on BW (low BW and high BW). Sheep within each block were then allotted to 9 pens respectively (two sheep/pen). Pens within each block were randomly assigned to one of three dietary treatments: (1) basal diet (CON); (2) basal diet + 40 mg/kg DM of MON; (3) basal diet + 274.5 mg/kg DM of NIS. The study lasted 9 weeks, with the initial 2 weeks for adaptation and the subsequent 7 weeks for treatment.
UNASSIGNED: The results showed that both NIS and MON addition had no impacts on average daily gain (ADG), dry matter intake (DMI), and feed conservation rate (G:F) of sheep (p > 0.05). The digestibility of ether extract (EE) was lower in the MON-fed and NIS-fed sheep (p < 0.01) than in the CON group, whereas crude protein (CP) digestibility was higher in the MON-fed sheep compared to those fed NIS (p < 0.05). Both NIS and MON supplementation decreased acetate levels and acetate/propionate ratio in the rumen of Hu sheep (p < 0.05). Sheep fed MON exhibited higher total cholesterol concentrations (p < 0.05) compared to the CON and NIS groups. However, there were no significant differences in other plasma metabolites, including blood urea nitrogen (BUN), total bile acid, triglyceride, total protein, albumin, globulin, glucose, etc., among the three groups (p > 0.05).
UNASSIGNED: In conclusion, dietary addition of NIS and MON altered the rumen fermentation mode by reducing acetate levels, with no discernible effects on the growth performance of the fattening Hu sheep.

A colloidal gold immunochromatographic assay (CGIA) based on single-chain variable fragments (scFvs) has been successfully developed for the detection of monensin (MON). Colloidal gold probes were conjugated to anti-MON scFvs through electrostatic interaction, with the conjugated objects serving as the visual signals. The detection lines were formed by capturing the antibody with MON-OVA. This assay offers a rapid detection time of 15 min, a wide linear range from 2.19 to 10.76 ng mL-1, and boasts high accuracy, precision, and an absence of cross-reactivity. By homology modeling and molecular docking, we predicted the interaction patterns between the scFv and monensin, and the amino acid residues involved in the recognition of MON by the antibody were analyzed. These key amino acid sites are presumed integral to ligand recognition per current interaction models. This hypothesis was confirmed by computer-aided alanine scanning mutation, MM/P(G)BSA molecular dynamics simulation, and in vitro binding experiments. In this study, we successfully developed the scFvs-based CGIA system for rapid and easy quantification of monensin, providing a simple, efficient routine detection of chicken muscle samples.

Despite intense efforts to develop efficient therapeutic regimes for asthma, there is a large demand for novel treatment strategies in this disease. Here we evaluated the impact of monensin, a drug with potent anti-mast cell effects, in a mouse model of asthma. Allergic airway inflammation was induced by sensitization of mice with house dust mite (HDM) antigen, and effects of monensin on airway hyperreactivity and inflammatory parameters were studied. Following intraperitoneal administration, monensin did not suppress airway hyperreactivity but was shown to have anti-inflammatory properties, as manifested by reduced eosinophil- and lymphocyte infiltration into the airway lumen, and by suppressed inflammation of the lung tissue. After intranasal instillation, monensin exhibited similar anti-inflammatory effects as seen after intraperitoneal administration. Moreover, intranasally administered monensin was demonstrated to suppress goblet cell hyperplasia, and to cause a reduction in the expression of genes coding for key inflammatory markers. Further, monensin blocked mast cell degranulation in the airways of allergen-sensitized mice. Together, this study reveals that monensin has the capacity to suppress key pathological events associated with allergic airway inflammation.

BACKGROUND: Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) are recognized as a highly challenging subset of cells, renowned for their heightened propensity for relapse and unfavorable prognosis. Monensin, an ionophoric antibiotic, has been reported to exhibit significant therapeutic efficacy against various cancers, especially CSCs. Erlotinib is classified as one of the EGFR-TKIs and has been previously identified as a promising therapeutic target for TNBC. Our research aims to assess the effectiveness of combination of monensin and erlotinib as a potential treatment strategy for TNBC.
METHODS: The combination of monensin and erlotinib was assessed for its potential anticancer activity through various in vitro assays, including cytotoxicity assay, colony formation assay, wound healing assay, transwell assay, mammosphere formation assay, and proportion of CSCs assay. Additionally, an in vivo study using tumor-bearing nude mice was conducted to evaluate the inhibitory effect of the monensin and erlotinib combination on tumor growth.
RESULTS: The results indicated that combination of monensin with erlotinib synergistically inhibited cell proliferation, the migration rate, the invasion ability and decreased the CSCs proportion, and CSC markers SOX2 and CD133 in vivo and in vitro. Furthermore, the primary proteins involved in the signaling pathways of the EGFR/ERK and PI3K/AKT are simultaneously inhibited by the combination treatment of monensin and erlotinib in vivo and in vitro.
CONCLUSIONS: The simultaneous inhibition of the EGFR/ERK and PI3K/AKT/mTOR signaling pathways by the combination of monensin and erlotinib exhibited a synergistic effect on suppressing tumor proliferation and cancer cell stemness in TNBC.

BACKGROUND: Endolysosomal compartments are acidic and contain low pH-dependent proteases, and these conditions are exploited by respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, for escaping into the cytosol. Moreover, endolysosomes contain various pattern recognition receptors (PRRs), which respond to virus-derived pathogen-associated molecular patterns (PAMPs) by production of proinflammatory cytokines/chemokines. However, excessive proinflammatory responses can lead to a potentially lethal cytokine storm.
OBJECTIVE: Here we investigated the endosomal PRR expression profile in primary human small airway epithelial cells (HSAECs), and whether blockade of endolysosomal acidification affects their cytokine/chemokine production after challenge with virus-derived stimulants.
METHODS: HSAECs were exposed to stimulants mimicking virus-derived PAMPs, either in the absence or presence of compounds causing blockade of endolysosomal acidification, followed by measurement of cytokine expression and release.
RESULTS: We show that Toll-like receptor 3 (TLR3) is the major endosomal PRR expressed by HSAECs, and that TLR3 expression is strongly induced by TLR3 agonists, but not by a range of other PRR agonists. We also demonstrate that TLR3 engagement with its agonists elicits a robust proinflammatory cytokine/chemokine response, which is profoundly suppressed through blockade of endolysosomal acidification, by bafilomycin A1, monensin, or niclosamide. Using TLR3 reporter cells, it was confirmed that TLR3 signaling is strongly induced by Poly(I:C) and that blockade of endolysosomal acidification efficiently blocked TLR3 signaling. Finally, we show that blockade of endolysosomal acidification causes a reduction in the levels of TLR3 mRNA and protein.
CONCLUSIONS: These findings show that blockade of endolysosomal acidification suppresses TLR3-dependent cytokine and chemokine production in HSAECs.

The exploration of natural alternatives to antibiotics for enhancing productivity and performance in dairy cows is a crucial objective in farm animal management. This is the first study aimed at developing and evaluating the physicochemical properties and effects of Arabic gum-nano montmorillonite (AGNM) compost compared to ionophore monensin as feed additives on rumen fermentation, blood metabolites, and milk production of Holstein dairy cows. In a replicated 4 × 4 Latin square design, four multiparous mid-lactation Holstein dairy cows with an average body weight of 520 ± 15 kg were enrolled. The dietary treatments included a control diet (basal diet without feed additives), monensin diet [a basal diet supplemented with 35 mg/kg dry matter (DM) monensin], and AGNM diets comprising basal diet supplemented with two levels: low (L-AGNM) at 1.5 g/kg DM, and high (H-AGNM) at 3 g/kg DM. AGNM as a feed additive demonstrated promising physiochemical parameters, including containing highly bioactive components (α-amyrin and lupeol), functional groups (OH and Si-O), and essential mineral contents (Mg2+). Supplementations with H-AGNM significantly improved ruminal (p = 0.031) concentrations of total volatile fatty acids (VFAs), acetic (p = 0.05) and butyric (p = 0.05), enhanced (p < 0.05) digestibility of fiber and organic matter, while decreased (p = 0.013) estimated methane production. However, an increase (p = 0.04) in blood high-density lipoprotein levels and decrease (p < 0.05) in concentrations of creatinine (CREA), bilirubin (BILT), cholesterol (CHOL), and sodium (Na) were observed with H-AGNM supplementation. Both monensin and H-AGNM improved (p = 0.008) feed efficiency compared to L-AGNM; however, neither AGNM nor monensin affected the milk composition or energy status indicators of the dairy cows. The findings of this study highlight the potential of AGNM as a natural candidate to replace monensin in enhancing ruminal VFA production, nutrient digestibility, feed efficiency, blood metabolites, and milk yield in dairy cows.

This experiment compared narasin and monensin as anticoccidials for calves naturally infected with Eimeria spp. Twenty-four weaned, non-castrated male calves (Bos indicus × B. taurus cross) were assigned to this experiment (days -8 to 42). All calves were infected by Eimeria spp. according to oocyst count per gram (OPG) from fecal samples collected on days -8 and -7 (average 1,059 ± 101 oocysts/g). Calves were housed in individual pens, received corn silage, mineral mix, and water for ad libitum consumption, in addition to a grain-based supplement at 200 g/head daily. Fecal samples were collected on days -2 and -1 for OPG, and results averaged as initial OPG value. Calves were blocked according to initial OPG into eight blocks of three calves each, ranked within each block according to body weight (BW) recorded on day -1, and assigned to receive narasin (NAR; 0.8 mg/kg of BW), monensin (MON; 1 mg/kg of BW), or no ionophore (CON; negative control). Ionophores were added to the grain-based supplement, and offered from days 0 to 42 of the experiment. Calf BW was recorded on days 7, 14, 21, 28, 35, and 42. Fecal samples were collected on days 6 and 7, 13 and 14, 20 and 21, 26 and 27, 34 and 35, and 41 and 42 for OPG analysis, and results from samples collected on consecutive days were averaged. Aliquoted fecal samples were also pooled across calves from the same treatment and collection days, and used to determine the prevalence of individual species of Eimeria. No treatment effects were detected (P ≥ 0.51) for calf BW or growth rate. A treatment × day interaction was detected (P < 0.01) for OPG, as NAR and MON calves had less (P < 0.01) OPG compared with CON calves beginning on day 7. The OPG was also less (P ≤ 0.03) in MON compared with NAR calves on days 7, 14, and 28, but did not differ (P ≥ 0.48) on days 21, 35, and 42. The anticoccidial efficacy of NAR and MON did not differ (P ≥ 0.16) when calculated across all Eimeria spp., or according to prevalence of E. bovis and E. alabamensins. A treatment × day interaction was detected (P = 0.04) for anticoccidial efficacy to E. alabamensis, which was greater (P < 0.01) in MON calves on days 7 and 14 and did not differ (P ≥ 0.40) afterward. Collectively, both ionophores were similarly effective in controlling coccidiosis upon completion of the 42-d study, although the anticoccidial effects of monensin were noted earlier in the experiment. Nonetheless, these results corroborate narasin as an efficient anticoccidial ionophore for naturally infected calves.

Monensin, an antibacterial commonly used in animal fattening, can enter aquatic ecosystems and harm non-target organisms. Since there are no previous studies about the effects of monensin on amphibians, the aim of the present study was to evaluate the lethal and sublethal toxicity of a commercial formulation of monensin (CFM) through standardized bioassays with embryos and larvae of the amphibian Rhinella arenarum. Oxidative stress (catalase and glutathione S-transferase activities, and reduced glutathione and lipid peroxidation levels), cholinesterasic effect (acetylcholinesterase and butyrylcholinesterase activities) and mutagenicity (micronuclei frequency) biomarkers were evaluated. The CFM produced teratogenic effects, with a teratogenic index of 6.21. Embryos (504 h-LC50: 273.33 µg/L) were more sensitive than larvae, as no significant mortality was observed on larvae exposed up to 3000 µg/L for 504 h. However, oxidative stress, cholinesterasic effect and mutagenicity biomarkers were altered on larvae exposed for 96 h to environmentally relevant concentrations (4, 12 and 20 µg/L of monensin active ingredient). The CFM caused adverse effects on the exposed organisms, primarily on embryos, leading to lethal and sublethal effects, which could impact the wildlife when it reaches aquatic ecosystems.

This study investigated the effects of the early administration of enrofloxacin (E) or doxycycline (D) for the first 5 consecutive days of life, or the continuous administration of the coccidiostat monensin (M) throughout the rearing period on gastrointestinal function in turkeys infected with avian pathogenic Escherichia coli (APEC) in an early or later stage of rearing. Experiment 1 lasted 21 d, and turkeys in groups E, D, and M were infected with APEC on d 15. Experiment 2 lasted 56 d, and it had a factorial arrangement of treatments where birds in groups E, D, and M were infected with APEC on d 15 or d 50. In both experiments, control groups (C) consisted of infected and uninfected birds without antibiotic or coccidiostat administration. On d 21 (Experiment 1) and d 56 (Experiment 2), 8 birds from each subgroup were killed, and the ileal and cecal digesta were sampled to analyze the activity of bacterial enzymes and the concentrations of short-chain fatty acids (SCFA). The experimental treatments did not affect the final body weight or body weight gain of birds. Both experiments demonstrated that APEC contributed to an increase in ammonia levels of the cecal digesta (means from 2 experiments: 0.311 vs. 0.225 mg/g in uninfected birds) and ileal pH (6.79 vs. 6.00) and viscosity (2.43 vs. 1.83 mPa⋅s). Moreover, the E. coli challenge enhanced the extracellular activity of several cecal bacterial enzymes, especially in older turkeys infected with APEC in a later stage of life. The continuous administration of monensin throughout the rearing period resulted in a weaker gastrointestinal response in older birds, compared with the other 2 antibiotics administered for the first 5 d of life. The results of the study are inconclusive as both desirable and undesirable effects of preventive early short-term antibiotic therapy were observed in turkeys, including normalization of ileal viscosity and cecal ammonia concentration (positive effect), and disruption in cecal SCFA production (negative effect).

Meta-analyses were performed to quantitatively summarize the effects of monensin on in vivo methane (CH4) production in beef cattle, and differentiate these outcomes according to dietary management, dose of monensin, and length of monensin supplementation. Data from 11 manuscripts describing 20 individual studies were used, and CH4 was converted to g/d when required. Studies were classified according to dose of monensin (mg/kg of diet dry matter), length of monensin supplementation prior to the last CH4 measurement, feeding management (ad libitum vs. limited-fed), and diet profile (high-forage or high-concentrate diets). Variance among studies were assessed using a χ² test of heterogeneity and calculated using I² statistics. The inclusion of monensin decreased (P < 0.01) CH4 production by 17.5 g/d when all studies were analyzed together. A moderate (P < 0.01) heterogeneity (I² = 55%) was detected for CH4 production estimates between studies; thus, meta-analyses were performed within classes. The reduction in CH4 differed (P < 0.01) according to dose of monensin, as it decreased (P < 0.01) by 25.6 g/d when the high recommended dose range was used (32 to 44 mg/kg), and tended to decrease (P ≤ 0.07) by 9.7 and 13.5 g/d when the moderate (≤31 mg/kg) and above recommended (≥45 mg/kg) doses were used, respectively. The reduction in CH4 also differed (P < 0.01) according to the length of monensin supplementation. Monensin decreased (P ≤ 0.05) CH4 production by 24.3 g/d when supplemented for <15 d, by 15.4 g/d when supplemented from 23 to 33 d, by 24.3 g/d when supplemented from 52 to 79 d, and tended to decrease (P = 0.06) CH4 production by 3.21 g/d when supplemented from 94 to 161 d. The reduction in CH4 did not differ (P = 0.37) according to diet profile, despite a 30% difference in reduction when monensin was added to high-forage (20.89 g/d) compared with high-concentrate diets (14.6 g/d). The reduction in CH4 tended to differ according to feeding management (P = 0.08), decreasing by 22.9 g/d (P < 0.01) when monensin was added to diets offered ad libitum, and by 11.5 g/d (P = 0.05) in limit-fed diets. Collectively, this study provides novel insights and further corroborates monensin as CH4 mitigation strategy in beef cattle operations. The most effective responses were observed during the first 79 d of monensin supplementation, and when monensin was included between 32 to 44 mg/kg of diet, was added to high-forage diets, and added to diets fed ad libitum.