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The abnormal activation of the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (EMT) in drug-resistant tumor cells and cancer stem cells (CSCs) stimulate tumor metastasis and recurrence. Here, a promising combined chemotherapeutic strategy of salinomycin (SL) and doxorubicin (DOX) with specific inhibition of tumor stemness by a targeted co-delivery nanosystem was developed to overcome this abnormal progression. This strategy could be benefit drugs to effectively penetrate and infiltrate into spheres of 3D-cultured breast cancer stem cells (BCSCs). The expression of the Wnt/β-catenin signaling pathway-related genes (β-catenin, LRP6, LEF1 , and TCF12) and target genes (Cyclin D1, Cmyc , and Fibronectin) as well as CSC stemness-related genes (Oct4, Nanog , and Hes1) was downregulated by redox-sensitive co-delivery micelles decorated with oligohyaluronic acid as the active targeting moiety. The changes in EMT-associated gene expression (E-cadherin and Vimentin) in vitro showed that the EMT process was also effectively inverted. This strategy achieved a strong inhibitory effect on solid tumor growth and an effective reduction in the risk of tumor metastasis in 4T1 tumor-bearing mice in vivo and effectively alleviated splenomegaly caused by the malignant tumor. Immunohistochemical staining analysis of E-cadherin, Vimentin, and β-catenin confirmed that the inversion of the EMT was also achieved in solid tumors. These results highlight the potential of SL and DOX combined chemotherapeutic strategy for eliminating breast carcinoma. Cancer stem cells (CSCs), as an important part of tumor heterogeneity, can survive against conventional chemotherapy and initiate tumorigenesis, recurrence, and metastasis. Moreover, non-CSCs can convert into the CSC state through the abnormal Wnt/β-catenin pathway, which is closely related to the epithelial-mesenchymal transition (EMT) process. Here, redox-degradable binary drug-loaded micelles (PPH/DOX+SL) were designed to target CSCs and overcome drug resistance of breast cancer cells. The combined chemotherapy of salinomycin (SL) and doxorubicin (DOX) reversed drug resistance, while the PPH/DOX+SL micelles enhanced the intracellular accumulation and drug penetration of BCSC spheres. The introduction of SL downregulated the expression of tumor stemness genes and the Wnt/β-catenin pathway-related genes and inverted the EMT process. PPH/DOX+SL continuously inhibited tumor growth and invasion in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

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Multistress effects lead to unpredicted consequences in aquatic ecotoxicology and are extremely concerning. The goal of this study was to trace how specific effects of the antibiotic salinomycin (Sal) and microplastics (MP) on the bivalve molluscs are manifested in the combined environmentally relevant exposures. Unio tumidus specimens were treated with Sal (0.6 μg L−1), MP (1 mg L−1, 2 μm size), and both at 18 °C (Mix) and 25 °C (MixT) for 14 days. The redox stress and apoptotic enzyme responses and the balance of Zn/Cu in the digestive gland were analyzed. The shared signs of stress included a decrease in NAD+/NADH and Zn/Cu ratios and lysosomal integrity and an increase in Zn-metallothioneins and cholinesterase levels. MP caused a decrease in the glutathione (GSH) concentration and redox state, total antioxidant capacity, and Zn levels. MP and Mix induced coordinated apoptotic/autophagy activities, increasing caspase-3 and cathepsin D (CtD) total and extralysosomal levels. Sal activated caspase-3 only and increased by five times Cu level in the tissue. Due to the discriminant analysis, the cumulative effect was evident in the combined exposure at 18 °C. However, under heating, the levels of NAD+, NADH, GSH, GSH/GSSG and metallothionein-related thiols were decreased, and coordination of the cytosolic and lysosomal death stimuli was distorted, confirming that heating and pollution could exert unexpected synergistic effects on aquatic life. [Display omitted] • Mussels exposed to salinomycin (Sal), microplastic (MP) and their combinations. • Common responses of NAD+/NADH, Zn/Cu, Zn-metallothionein. • MP alone causes the most noticeable damage. • All exposures without heating activate caspase-3 and (except Sal) cathepsin D. • The cumulative effect of the mixture and its distortion under the heating were detected. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the effects of salinomycin (Sal) on expressions of baculoviral IAP repeat- containing 5 (BIRC5) and Nei endonuclease VIII-like 2 (NEIL2) and radiotherapy sensitivity of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Human NPC CNE-2 cell lines were used as research objects in this study. Subsequently, the cells received intervention with Sal at different concentrations, radioactive rays at different doses and Sal combined with radioactive rays. The growth inhibition rate of CNE-2 cells was detected via methyl thiazolyl tetrazolium (MTT) assay. The dose-effect relations of Sal, radioactive rays and combination therapy with the inhibitory effect on CNE-2 cells were obtained. CNE-2 cells receiving intervention with Sal at an appropriate concentration or radioactive rays at an appropriate dose alone and Sal combined with radioactive rays were used as intervention groups (Sal group, Radiation group and Combination group). However, those added with an equal amount of DMSO were set as Control group. Next, the cycle, apoptosis and apoptotic morphology of CNE-2 cells were observed via flow cytometry and Hoechst assay, respectively. Moreover, the expressions of apoptosis-related proteins Caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax), as well as BIRC5 and NEIL2 proteins in CNE-2 cells were determined using Western blotting. RESULTS: Under the intervention with Sal or radioactive rays alone, the growth inhibition rate of CNE-2 cells rose in a concentration/dose-dependent manner. With the increase in Sal concentration in combination therapy, the growth inhibition rate of CNE-2 cells significantly increased (p<0.05). Compared with Control group, Sal group, Radiation group, and Combination group exhibited remarkably lower colony formation rate, higher proportion of CNE-2 cells in the G2/M phase, enhanced apoptosis of CNE-2 cells with nuclear fragmentation, increased expressions of pro-apoptotic proteins Caspase-3 and Bax, decreased expression of anti-apoptotic protein Bcl-2, and lower protein expressions of BIRC5 and NEIL2 in cells (p<0.05). Compared with Radiation group, the Combination group had significantly decreased colony formation rate, increased proportion of CNE-2 cells in the G2/M phase, enhanced apoptosis of CNE-2 cells with more nuclear fragmentation and other apoptosis characteristics, increased expressions of pro-apoptotic proteins Caspase-3 and Bax, decreased expression of anti-apoptotic protein Bcl-2, and decreased protein expressions of BIRC5 and NEIL2 in cells (p<0.05). CONCLUSIONS: Sal enhances the radiotherapy sensitivity of NPC and reduces the protein expressions of BIRC5 and NEIL2 in cells. [ABSTRACT FROM AUTHOR]

Abstract Nanoscale drug delivery system (NDDS) with slow premature drug release (PDR) while ensuring burst intracellular drug release (BIDR) is becoming a hot point in NDDS-based nanomedicine. Here we used clathrin to modify a solid lipid nanoparticle (SLN)-based NDDS of salinomycin (SLN-SAL) to prepare NDDS with reduced PDR while ensuring BIDR. Drug-release-kinetic experiments revealed that clathrin modified SLN-SAL (CMSLN-SAL) reduced PDR while ensured BIDR of its prototype NDDS, SLN-SAL. Mechanism experiments revealed that clathrin modification reduced PDR of SLN-SAL through increasing the mechanical strength of SLN-SAL and ensured BIDR of SLN-SAL through lipid membrane fusion after its clathrin shell was de-polymerized by a cytoplasm enzyme, HSC70. In addition, CMSLN-SAL had significantly higher intracellular uptake and stronger inhibitive effects on cancer cells than that of SLN-SAL. These results demonstrated that clathrin modification is an effective way to reduce PDR while ensuring BIDR and increasing the anticancer effects of SLN-based NDDS. Graphical abstract The clathrin-shell of clathrin-modified solid lipid nanoparticle-based nanoscale drug delivery system of salinomycin (CMSLN-SAL) works as a cable net to resist internal osmotic pressure to block particle expending and as a cage-like scaffold to resist external pressure exerted by the blood flow at the artery bifurcation and the mouth piece of vascular clefts to block particle deformation, and thereby to reduce the drug loss in transportation, namely, the premature drug release. In tumor cells, the clathrin shell of CMSLN-SAL is depolymerized by HSC70 and the inner SLN-SAL is freed in cytosol to ensure the intracellular burst drug release. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract Cadmium (Cd) is an environmental pollutant shown to induce multi organ dysfunction. In this study we present novel data about the effects of meso -2,3-dimercaptosuccinic acid (DMSA), monensin and salinomycin on the concentration of Cd in skeletal muscles of mice exposed to Cd (II) acetate treatment for 14 days. The impact of Cd and the chelating agents on the endogenous concentrations of calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorous (P), selenium (Se) and zinc (Zn) was also investigated. Subacute exposure of mice to Cd (II) acetate resulted in a significant accumulation of the toxic metal ion in the skeletal muscles compared to the untreated controls. Salinomycin most effectively mobilized Cd from the muscles compared to DMSA and monensin. The Cd exposure and the tested chelating agents did not significantly alter the endogenous concentrations of the selected essential elements in mouse muscles. The presented results confirmed that among the tested chelating agents salinomycin is superior as a potential antidote to Cd poisoning. [ABSTRACT FROM AUTHOR]

Abstract We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma. Graphical Abstract The mechanism of the superior targeting efficacy of CESP in osteosarcoma cells. Unlabelled Image [ABSTRACT FROM AUTHOR]

Copyright of Revue de Médecine Vétérinaire is the property of Ecole Nationale Veterinaire de Toulouse and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The varied therapeutic approaches like radiotherapy, chemotherapy, surgery, etc. primarily aimed to target cancer cells specifically. Despite these efforts, they are not completely successful in eliminating this deadly pathological state. These failures ultimately lead to cancer reoccurrence, which is again, another burning problem associated with cancer. The prime reason for the above observation has been found to be the development of resistance by cancer cells towards cancer drugs or cancer-initiating cells (cancer stem cells) remain unaffected by existing treatment procedures. Recent research has evolved two drugs, salinomycin and apoptin, that hold great potential for the future of cancer treatment not only for restricting malignancy, but also in preventing tumor recurrence. The present review article will put light on these new upcoming cancer stem cell targeting agents. [ABSTRACT FROM AUTHOR]

Copyright of Veterinary Archives / Veterinarski Arhiv is the property of University of Zagreb, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys > spleen > liver > brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs. [ABSTRACT FROM AUTHOR]

A total of thirty suspected broiler chicks were screened for coccidiosis, of them 25 chicks were found to be infected with coccidiosis viz. Eimeria tenella (15) Eimeria maxima (5) Eimeria necatrix (6) and Eimeria mitis (4). The anticoccidial efficacy of Azadirachta indica and Carica papaya with Salinomycin as a dietary feed supplement on the representative E. tenella (25X10³ oocyst) infection challenged in broiler chicks was studied in six groups for the period of six weeks. A. indica and C. papaya leaves were administered in powder form at the concentration of 0.1% and 0.2% respectively. The Oocysts per gram (OPG) count were observed on 8th, 9th, 10th, 11th day of post inoculation (DPI). The challenged experimental chicks revealed haemorrhage, thickening of mucosa, cores of blood and ballooning of caecum. The experimental group T5 chicks treated with A. indica were analyzed to possess the maximum weight gain (2.003), better feed conversion ratio (FCR) (2.32), OPG count (5.87), livability percentage (88) and the lesion score (3.33). Chisquare test analysis revealed no significant differences among the treated groups and the performance parameters. Therefore, this study concludes that plant sources used as a remedial curate for coccidiosis is a perforated growth in the commercial broiler industries. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelial–mesenchymal transition (EMT), and to provide experimental basis for the treatment of urological tumors. Methods The bladder cancer cell line T24 was cultured in vitro . The rat bladder tumor model was established in vivo . The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of mRNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6 ( P < 0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h ( P < 0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h ( P < 0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group ( P < 0.05). The serum mRNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group ( P < 0.05). Conclusions Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells. [ABSTRACT FROM AUTHOR]

The occurrence, bioaccumulation, and human dietary exposure via seafood consumption of 37 antibiotics in six typical marine aquaculture farms surrounding Hailing Island, South China were investigated in this study. Sulfamethoxazole, salinomycin and trimethoprim were widely detected in the water samples (0.4–36.9 ng/L), while oxytetracycline was the predominant antibiotic in the water samples of shrimp larvae pond. Enrofloxacin was widely detected in the feed samples (16.6–31.8 ng/g) and erythromycin–H 2 O was the most frequently detected antibiotic in the sediment samples (0.8–4.8 ng/g). Erythromycin–H 2 O was the dominant antibiotic in the adult Fenneropenaeus penicillatus with concentrations ranging from 2498 to 15,090 ng/g. In addition, trimethoprim was found to be bioaccumulative in young Lutjanus russelli with a median bioaccumulation factor of 6488 L/kg. Based on daily intake estimation, the erythromycin–H 2 O in adult F. penicillatus presented a potential risk to human safety. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Elementology is the property of Journal of Elementology - issued by Polish Magnesium Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chemical Industry / Hemijska Industrija is the property of Association of Chemical Engineers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses a study which aimed to determine the effect of salinomycin and sodium fumarate on rumen fermentation. The findings show that salinomycin reduced the digestibility of basal ration at low doses while sodium fumarate tended to have an opposite effect. It also reveals that only salinomycin produced a dose-dependent decrease in protozoal count.

The article offers information on a study which described an outbreak of salinomycin poisoning in rabbits.

The article discusses a study which determined the presence of pathogen Clostridium (C.) perfringens by polymerase chain reaction (PCR) and DNA sequencing, without previous cultivation, and investigated how C. perfringens was affected by different preventive measures for necrotic enteritis in broilers chickens. DNA extraction kits were used to extract DNA from the intestinal content or intestinal tissue and samples were obtained from single conventional broilers or from pools of six birds of experimentally reared broilers. Results showed that conventional chickens given salinomycin in their feed have reduced numbers of C. perfringens-positive samples for all PCR tests and the addition of sodium butyrate and lactic acid in the birds' feed had a minor effect on positive samples.

Abstract: The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC50-values between 2.4 and 19.6μM were obtained; however, one compound, nicarbazin exhibited an EC50-value above the maximum tested concentration (21μM, 9.1mgL−1). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC50-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT50 of 4.1 days) and was unstable at low pH (DT50 of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. [Copyright &y& Elsevier]

The article discusses a study which examined the effect of different feed additives supplementation on rumino-reticular motility in buffalo calves. Topics covered include the usefulness of salinomycin and Urea Molasses Mineral Block (UMMB) in enhancing the digestive efficiency of ruminants, and the potential effect of such feed additives in cases of rumen dysfunctions.

Coronavirus disease outbreak caused a severe public health burden all over the world. Salinomycin (SAL) is a broad-spectrum antibiotic that had drawn attention in selective targeting of cancer and viral infections. Recent drug screen identified SAL as a potent antiviral agent against SARS-CoV-2. In this hypothesis, we discuss the potential of pulmonary delivery of SAL using nanostructured lipid carriers (NLCs) against SARS-CoV-2. [ABSTRACT FROM AUTHOR]