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Microbiology Spectrum Aug 2023Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were...
Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were reported globally, with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern. The supply of MPXV vaccines is limited, and only two antivirals, tecovirimat and brincidofovir, approved by the U.S. Food and Drug Administration (FDA) for the treatment of smallpox, are currently available for the treatment of MPXV infection. Here, we evaluated 19 compounds previously shown to inhibit different RNA viruses for their ability to inhibit orthopoxvirus infections. We first used recombinant vaccinia virus (rVACV) expressing fluorescence (mScarlet or green fluorescent protein [GFP]) and luciferase (Nluc) reporter genes to identify compounds with antiorthopoxvirus activity. Seven compounds from the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, pyrazofurin, mycophenolate mofetil, azaribine, and brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed inhibitory activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, mycophenolate mofetil, and brequinar) and all the compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) were confirmed with MPXV, demonstrating their inhibitory activity against two orthopoxviruses. Despite the eradication of smallpox, some orthopoxviruses remain important human pathogens, as exemplified by the recent 2022 monkeypox virus (MPXV) outbreak. Although smallpox vaccines are effective against MPXV, access to those vaccines is limited. In addition, current antiviral treatment against MPXV infections is limited to the use of the FDA-approved drugs tecovirimat and brincidofovir. Thus, there is an urgent need to identify novel antivirals for the treatment of MPXV infection and other potentially zoonotic orthopoxvirus infections. Here, we show that 13 compounds, derived from two different libraries, previously found to inhibit several RNA viruses, also inhibit VACV. Notably, 11 compounds also displayed inhibitory activity against MPXV.
Topics: Humans; Mpox (monkeypox); Mycophenolic Acid; Smallpox; Antimycin A; Monensin; Rotenone; Valinomycin; Monkeypox virus; Antiviral Agents
PubMed: 37278625
DOI: 10.1128/spectrum.04745-22 -
Veterinary Medicine and Science Sep 2023Grazing in arid and semi-arid regions faces pregnant ewes with feed restrictions and hence affects the offspring muscle fibre characteristics. Using feed additives that...
Restricted maternal nutrition and supplementation of propylene glycol, monensin sodium and rumen-protected choline chloride during late pregnancy does not affect muscle fibre characteristics of offspring.
BACKGROUND
Grazing in arid and semi-arid regions faces pregnant ewes with feed restrictions and hence affects the offspring muscle fibre characteristics. Using feed additives that enhance nutrient availability during foetal muscle development is expected to alter offspring skeletal muscle characteristics.
OBJECTIVES
This study evaluated the effect of maternal restricted nutrition and supplementation of propylene glycol, monensin sodium and rumen-protected choline chloride on lamb's muscle fibre characteristics.
METHODS
Forty-eight Ghezel ewes were randomly allocated to one of six diets (N = 8) during the last 6 weeks of gestation: ad libitum feed intake (AL); restricted feeding (RF); restricted feeding containing propylene glycol (PG); restricted feeding containing propylene glycol and monensin sodium (MS); restricted feeding containing propylene glycol and rumen-protected choline chloride (RPC); restricted feeding containing propylene glycol, monensin sodium and rumen-protected choline chloride (PMC). The muscle samples were obtained from the semitendinosus muscle of 2-week-old male lambs (n = 5/treatment) via biopsy and were stained and classified as fibre types I, IIA and IIB.
RESULTS
Pre-parturient maternal feed restriction and administration of propylene glycol, monensin sodium and rumen-protected choline chloride had no significant effect on fibre-type composition, fibre density of muscle, muscle cross-sectional area and volume density of fibres (p > 0.05).
CONCLUSIONS
Either maternal dietary restriction or supplementation of nutrient flux-involved additives during late pregnancy did not alter muscle fibre development and had no short-term effects on muscle properties of the resulting offspring as myogenesis occurs in early and mid-gestation, not late gestation. Therefore, maternal nutrition may not be a problematic issue in sheep production in arid and semi-arid areas.
Topics: Pregnancy; Animals; Sheep; Female; Male; Monensin; Choline; Rumen; Propylene Glycol; Muscle Fibers, Skeletal; Dietary Supplements
PubMed: 37556348
DOI: 10.1002/vms3.1239 -
International Journal For Parasitology.... Aug 2023Worldwide distributed coccidiosis is caused by infection of both Eimeria species and Cystoisospora in the host intestine and causes huge economic losses to the livestock...
Worldwide distributed coccidiosis is caused by infection of both Eimeria species and Cystoisospora in the host intestine and causes huge economic losses to the livestock industry, especially the poultry industry. The control of such diseases relies mainly on chemoprophylaxis with anticoccidials, which has led to a very common drug resistance in this field. However, the genetic mechanisms underlying resistance to many anticoccidial drugs remain unknown. In this study, strains of E. tenella resistant to 250 mg/kg monensin were generated and characterized. Forward genetic approaches based on pooled genome sequencing, including experimental evolution and linkage group selection, were used to locate candidate targets responsible for resistance to monensin and diclazuril in E. tenella. A total of 16 nonsynonymous mutants in protein-coding genes were identified in monensin-resistant strains, and two genomic regions with strong selection signals were also detected in diclazuril-resistant strains. Our study reveals the genetic characterization of the experimental evolution and linkage group selection in Eimeria species, and also provides important information that contributes to the understanding of the molecular mechanism of drug resistance in coccidia.
Topics: Animals; Monensin; Eimeria tenella; Coccidiostats; Chickens; Poultry Diseases; Coccidiosis; Eimeria
PubMed: 37247559
DOI: 10.1016/j.ijpddr.2023.05.002 -
Molecules (Basel, Switzerland) Jun 2023The largely uncharted complexation chemistry of the veterinary polyether ionophores, monensic and salinomycinic acids (HL) with metal ions of type M and the known...
The largely uncharted complexation chemistry of the veterinary polyether ionophores, monensic and salinomycinic acids (HL) with metal ions of type M and the known antiproliferative potential of antibiotics has provoked our interest in exploring the coordination processes between MonH/SalH and ions of Ce. (1) Methods: Novel monensinate and salinomycinate cerium(IV)-based complexes were synthesized and structurally characterized by elemental analysis, a plethora of physicochemical methods, density functional theory, molecular dynamics, and biological assays. (2) Results: The formation of coordination species of a general composition [CeL(OH)] and [CeL(NO)(OH)], depending on reaction conditions, was proven both experimentally and theoretically. The metal(IV) complexes [CeL(NO)(OH)] possess promising cytotoxic activity against the human tumor uterine cervix (HeLa) cell line, being highly selective (non-tumor embryo Lep-3 vs. HeLa) compared to cisplatin, oxaliplatin, and epirubicin.
Topics: Humans; Monensin; Cerium; Ionophores; Ions
PubMed: 37375231
DOI: 10.3390/molecules28124676 -
Clinical and Translational Science Sep 2023Monensin is an ionophore antibiotic that inhibits the growth of cancer cells. The aim of this study was to investigate the apoptosis-mediated anticarcinogenic effects of...
Monensin is an ionophore antibiotic that inhibits the growth of cancer cells. The aim of this study was to investigate the apoptosis-mediated anticarcinogenic effects of monensin in SH-SY5Y neuroblastoma cells. The effects of monensin on cell viability, invasion, migration, and colony formation were determined by XTT, matrigel-chamber, wound healing, and colony formation tests, respectively. The effects of monensin on apoptosis were determined by real-time polymerase chain reaction, TUNEL, Western blot, and Annexin V assay. We have shown that monensin suppresses neuroblastoma cell viability, invasion, migration, and colony formation. Moreover, we reported that monensin inhibits cell viability by triggering apoptosis of neuroblastoma cells. Monensin caused apoptosis by increasing caspase-3, 7, 8, and 9 expressions and decreasing Bax and Bcl-2 expressions in neuroblastoma cells. In Annexin V results, the rates of apoptotic cells were found to be 9.66 ± 0.01% (p < 0.001), 29.28 ± 0.88% (p < 0.01), and 62.55 ± 2.36% (p < 0.01) in the 8, 16, and 32 μM monensin groups, respectively. In TUNEL results, these values were, respectively; 35 ± 2% (p < 0.001), 34 ± 0.57% (p < 0.001), and 75 ± 2.51% (p < 0.001). Our results suggest that monensin may be a safe and effective therapeutic candidate for treating pediatric neuroblastoma.
Topics: Humans; Child; Neuroblastoma; Monensin; Annexin A5; Apoptosis; Cell Line, Tumor; Cell Proliferation
PubMed: 37477356
DOI: 10.1111/cts.13593 -
Journal of Animal Science and... Jan 2024Stocker cattle diet and management influence beef cattle performance during the finishing stage, but knowledge of the dynamics of the rumen microbiome associated with...
BACKGROUND
Stocker cattle diet and management influence beef cattle performance during the finishing stage, but knowledge of the dynamics of the rumen microbiome associated with the host are lacking. A longitudinal study was conducted to determine how the feeding strategy from the stocker to the finishing stages of production affects the temporal dynamics of rumen microbiota. During the stocker phase, either dry hay or wheat pasture were provided, and three levels of monensin were administrated. All calves were then transported to a feedlot and received similar finishing diets with or without monensin. Rumen microbial samples were collected on d 0, 28, 85 during the stocker stage (S0, S28 and S85) and d 0, 14, 28, 56, 30 d before slaughter and the end of the trial during the finishing stage (F0, F14, F28, F56, Pre-Ba, and Final). The V4 region of the bacterial 16S rRNA gene of 263 rumen samples was sequenced.
RESULTS
Higher alpha diversity, including the number of observed bacterial features and the Shannon index, was observed in the stocker phase compared to the finishing phase. The bacterial amplicon sequence variants (ASVs) differentiating different sampling time points were identified. Dietary treatments during the stocker stage temporally impact the dynamics of rumen microbiota. For example, shared bacteria, including Bacteroidales (ASV19) and Streptococcus infantarius (ASV94), were significantly higher in hay rumen on S28, S85, and F0, while Bacteroidaceae (ASV11) and Limivicinus (ASV15) were more abundant in wheat. Monensin affected rumen microbial composition at a specific time. Transportation to feedlot significantly influenced microbiome structure and diversity in hay-fed calves. Bacterial taxa associated with body weight were classified, and core microbiotas interacted with each other during the trial.
CONCLUSIONS
In summary, the temporal dynamics of the rumen microbiome in cattle at the stocker and finishing stage are influenced by multiple factors of the feeding strategy. Diet at the stocker phase may temporarily affect the microbial composition during this stage. Modulating the rumen microbiome in the steers at the stocker stage affects the microbial interactions and performance in the finishing stage.
PubMed: 38273357
DOI: 10.1186/s40104-023-00967-5 -
Journal of Dairy Science Dec 2023The objective of this study was to compare cashew nutshell extract (CNSE) to monensin and evaluate changes in in vitro mixed ruminal microorganism fermentation, nutrient...
The objective of this study was to compare cashew nutshell extract (CNSE) to monensin and evaluate changes in in vitro mixed ruminal microorganism fermentation, nutrient digestibility, and microbial nitrogen outflow. Treatments were randomly assigned to 8 fermenters in a replicated 4 × 4 Latin square design with 4 experimental periods of 10 d (7 d for diet adaptation and 3 d for sample collection). Basal diets contained 43.5:56.5 forage: concentrate ratio and each fermenter was fed 106 g of DM/d divided equally between 2 feeding times. Treatments were control (CON, basal diet without additives), 2.5 μM monensin (MON), 0.1 mg CNSE granule/g DM (CNSE100), and 0.2 mg CNSE granule/g DM (CNSE200). On d 8 to10, samples were collected for pH, lactate, NH-N, volatile fatty acids (VFA), mixed protozoa counts, organic matter (OM), and neutral detergent fiber (NDF) digestibility. Data were analyzed with the GLIMMIX procedure of SAS. Orthogonal contrasts were used to test the effects of (1) ADD (CON vs. MON, CNSE100, and CNSE200); (2) MCN (MON vs. CNSE100 and CNSE200); and (3) DOSE (CNSE100 vs. CNSE200). We observed that butyrate concentration in all treatments was lower compared with CON and the concentration for MON was lower compared with CNSE treatments. Protozoal population in all treatments was lower compared with CON. No effects were observed for pH, lactate, NH-N, total VFA, OM, or N utilization. Within the 24-h pool, protozoal generation time, tended to be lower, while NDF digestibility tended to be greater in response to all additives. Furthermore, the microbial N flow, and the efficiency of N use tended to be lower for the monensin treatment compared with CNSE treatments. Overall, our results showed that both monensin and CNSE decreased butyrate synthesis and protozoal populations, while not affecting OM digestibility and tended to increase NDF digestibility; however, such effects are greater with monensin than CNSE nutshell.
Topics: Animals; Monensin; Fermentation; Anacardium; Rumen; Digestion; Diet; Fatty Acids, Volatile; Butyrates; Lactates; Animal Feed
PubMed: 37678783
DOI: 10.3168/jds.2023-23597 -
Translational Animal Science Jan 2023The objective of this study was to compare the influence of beef production systems using additive combinations of growth-promotant technologies on meat quality. Steer...
The objective of this study was to compare the influence of beef production systems using additive combinations of growth-promotant technologies on meat quality. Steer calves ( = 120) were assigned to 1 of 4 treatments: 1) no technology (NT; control), 2) antibiotic treated (ANT; NT plus therapeutic antibiotics, monensin, and tylosin), 3) implant treated (IMP; ANT plus a series of three implants), and 4) beta-agonist treated (BA; IMP plus ractopamine-HCl). Muscle biopsy samples from the longissimus lumborum were extracted from a subset ( = 4 per treatment) of steers to evaluate expression of calpain-1, calpain-2, and calpastatin using real-time RT-PCR. Following carcass chilling, objective color (*, *, and *) was evaluated. The right strip loin was removed from each carcass, portioned into 2.54-cm steaks, and designated to 7, 14, or 21 d postmortem aging periods for analysis of cook loss and Warner-Bratzler shear force (). The anterior face of each strip loin was used for analysis of crude fat and moisture. Treatment influenced ( < 0.001) *, *, and *. The NT and IMP treatments had greater ( < 0.01) * values, ANT was intermediate, and BA had the lowest ( < 0.01) * values. The NT and IMP treatments had higher ( < 0.01) * and * values compared with ANT, which were higher ( < 0.01) than BA. Steaks from implanted steers (IMP and BA) tended ( ≤ 0.067) to exhibit higher * and * than steaks from nonimplanted steers. Cattle in the NT and ANT treatments produced steaks with increased ( < 0.01) crude fat percentage compared with the IMP and BA treatments, which were similar ( > 0.05). Percent moisture of NT steaks was lower ( < 0.01) than all other treatments, ANT was intermediate, and IMP and BA were similar ( > 0.05) and had the highest ( < 0.01) moisture content. Cook loss tended to be greater ( = 0.088) for implanted steers (IMP and BA) compared to nonimplanted steers (NT and ANT). Steaks from NT and ANT treatments were more tender ( < 0.05) than IMP and BA, which were similar ( > 0.05). Thus, WBSF was lower ( < 0.001) in nonimplanted than implanted steaks. Expression of calpastatin was increased ( ≤ 0.025) in ANT and BA treatments, and there was a tendency for expression of calpain-2 to be increased ( = 0.081) in ANT compared to NT. These results suggest that production systems with limited use of growth promoting technology produced strip loins with more crude fat, less moisture and cook loss, and improved tenderness.
PubMed: 37583488
DOI: 10.1093/tas/txad092 -
Journal of Dairy Science Feb 2024The objective of this study was to evaluate the effects of supplementing monensin (MON:19.8 g/Mg DM TMR) and Saccharomyces cerevisiae CNCM I-1077 (LCY: Saccharomyces...
The objective of this study was to evaluate the effects of supplementing monensin (MON:19.8 g/Mg DM TMR) and Saccharomyces cerevisiae CNCM I-1077 (LCY: Saccharomyces cerevisiae CNCM I-1077; 1 × 10 cfu/hd/d) on lactation performance, feeding behavior, and total-tract nutrient digestibility of high-producing dairy cows. Sixty-four multiparous Holstein cows (3.2 ± 1.5 lactations; 97 ± 16 DIM, and 724 ± 68 kg of BW at covariate period initiation) and 32 gate feeders were enrolled in a study with a completely randomized design and a 2 × 2 factorial arrangement. Cows and gate feeders were randomly assigned to treatments (16 cows and 8 gate feeds per treatment). Cows were allowed 2 wk to acclimate to feeding gates followed by a 2 wk covariate period. During the acclimation and covariate periods, all cows were fed a diet containing MON and LCY. Following the covariate period, cows were enrolled in a 10 wk treatment period during which cows were randomly assigned to 1 of 4 treatments: 1) a combination of MON and LCY (MON-LCY), 2) MON alone, 3) LCY alone, or 4) neither MON nor LCY (CON-CON). Data were analyzed using a mixed model with week as a repeated measure and fixed effects of MON, LCY, week, and all their interactions. Cow (treatment) was included as a random effect. The average covariate period value of each variable was used as a covariate. Three-way interactions were observed for DMI and feed efficiency. Dry matter intake decreased from wk 4-5 and 8-10 in MON-LCY cows compared with CON-CON. No treatment differences were observed for actual or component-corrected milk yield or milk components, except for a tendency for LCY to decrease milk fat yield. Feed efficiency was greater for MON-LCY relative to CON-CON in 4 of 10 weeks. Interactions between MON and LCY were observed for dry matter and organic matter digestibility, where both were lower for CON-CON than other treatments. Under the conditions of the present study, feeding dairy cows in a high feed bunk density a combination of MON and LCY can decrease intake and improve feed efficiency without affecting milk production or components. Additionally, monensin and live-cell yeasts may each improve total-tract digestibility based on improvements in dry matter and organic matter digestibility.
PubMed: 38331184
DOI: 10.3168/jds.2023-24125 -
Animals : An Open Access Journal From... Jul 2023Four experiments were conducted to evaluate sources of anti-coccidial compounds and phytogenic saponin extracts on in vitro and in vivo ruminal fermentation and CH...
Four experiments were conducted to evaluate sources of anti-coccidial compounds and phytogenic saponin extracts on in vitro and in vivo ruminal fermentation and CH production at multiple inclusion levels. In experiment 1, eight steers were fed either a finishing diet or a finishing diet supplemented with 0.5 mg/kg BW decoquinate (DCQ) and 3.33 mg/kg BW extract (YSE), and respiratory gas exchange was measured. In experiment 2, four ruminally-cannulated steers were fed the same treatments as experiment 1, and ruminal fermentation was evaluated. Anti-coccidial sources (experiment 3; monensin, DCQ, amprolium) and saponin sources (experiment 4; YSE, extract) and levels were evaluated for effects on in vitro ruminal fermentation and CH production. DCQ + YSE supplementation did not influence ( ≥ 0.24) in vivo respiratory gas consumption/production, in situ DM degradation, or liquid passage kinetics. Ruminal propionate proportion tended to increase ( = 0.09) with DCQ + YSE. Monensin decreased ( ≤ 0.04) in vitro acetate:propionate and CH production; saponin supplementation linearly increased ( < 0.01) propionate proportion but did not influence ( ≥ 0.38) in vitro CH production. Saponins and non-antibiotic anti-coccidials did not influence in vitro or in vivo CH production with finishing diets.
PubMed: 37508084
DOI: 10.3390/ani13142308