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Background: Repeat‐breeder cows repeatedly fail to conceive after at least three attempts and return to oestrus at apparently normal intervals. Repeat‐breeder cows cause economic losses in dairy farms in different ways. Objective: In the present study, we investigated the effect of sustained‐release progesterone injection in two different doses on the expression of interferon‐related genes in repeat‐breeder dairy cows. Methods: A total of 96 repeat‐breeder primiparous and multiparous cows were assigned among three groups: control group, inseminated and do not receive progesterone treatment; P400 and P600 groups, inseminated and received a single‐intramuscular injection of 400 and 600 mg slow‐release progesterone 5 days after insemination, respectively. Blood sampling was carried out on Day 20 after AI for progesterone measurement and evaluation of gene expression for ISG15, MX1 and MX2 genes. Results: One injection of sustained‐release progesterone increased the expression of ISG15, MX1 and MX2 genes with differences between two different progesterone concentrations. For all three genes, the level of gene expression was higher in progesterone‐supplemented group than in control group, when P400 and P600 groups considered together. The level of MX2 gene expression was significantly higher in pregnant cows than non‐pregnant cows. There was a significant positive correlation between expression level of all three genes and blood progesterone concentration. The expression level of ISG15 gene showed a significant positive correlation with MX1 and MX2 gene expression. Conclusion: The use of this sustained‐release progesterone is simple and can be used in repeat‐breeder cows to improve fertility. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257). Materials and Methods: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry. Results: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 μM for celastrol, 20.7 and 11.6 μM for 5-FU, and 5.03 and 4.57 μM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase. Conclusions: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol. [ABSTRACT FROM AUTHOR]

In this study, a controlled released delivery drug system designed and synthesized by loading curcumin and selenium nanoparticles (SeNaPs) on chitosan hydrogel, and while evaluating the physicochemical properties of the prepared drug delivery system, the tissue changes caused by the local implant of that system in rats with experimental spinal cord injury (SCI) were investigated. For this purpose, 100 adult female rats were randomly divided into five equal groups which are: Control group without any treatment for SCI, chitosan group that received chitosan hydrogel, curcumin group that received curcumin-loaded hydrogel, SeNaP group that received chitosan loaded with SeNaPs and SeNPCur group that received chitosan loaded with SeNaPs and curcumin. On the 3rd and 7th days of the study, severe infiltration of leukocytes, especially lymphocytes, as well as axon swelling and hemorrhagic necrosis at the lesion sites were observed in all groups, especially the control group. On the 7th day, the severity of these injuries decreased in the SeNPCur group and the highest number of astrocytes was observed in this group. In addition, on the 14th and 21st days of the study, the lowest severity of nerve tissue damage and the lowest presence of inflammatory cells along with the highest number of astrocytes were seen in the SeNPCur group. The glial fibrillary acidic protein study also confirmed the presence of more and significant astrocytes in the SeNPCur, curcumin and SeNP groups at different times of the study, respectively. The histopathological results showed the neuroprotective effects of chitosan hydrogel loaded with selenium and curcumin. [ABSTRACT FROM AUTHOR]

Background: In the present study, the effectiveness of a controlled-release drug delivery system of chitosan hydrogel loaded with ketorolac and buprenorphine on oxidative stress indices and albumin changes in the experimental bone defect model was considered. Methods: After creating an experimental defect in the right tibia of each rat, 5 groups, including (A) the control group that did not receive any pharmacological intervention, (B) the chitosan hydrogel receiving group, (C) the group receiving chitosan hydrogel loaded with buprenorphine, (D) the group receiving chitosan hydrogel loaded with ketorolac, and (E) the group receiving chitosan hydrogel loaded with ketorolac and buprenorphine, were considered. Serum concentrations of antioxidant factors and albumin levels were then measured on days 0, 3, 7, and 21 after surgery. Results: In the control group, the maximum amount of oxidative stress and the maximum activity of antioxidant enzymes on the third and seventh days were compared between the 4 treatment groups. Moreover, the maximum amount of albumin on the third day was recorded and compared between the 4 other treatment groups. In 4 treatment groups, a significant decrease was observed in the mean of parameters related to oxidative stress compared to the control group, which was more noticeable in the group receiving ketorolac. Conclusion: In the present study, the highest rate of control of oxidative stress conditions was observed in the group treated with the ketorolac-loaded chitosan hydrogel system, possibly due to its antioxidant properties and better control of inflammatory conditions caused by the use of chitosan and ketorolac in this treatment group. [ABSTRACT FROM AUTHOR]

This study was aimed at developing a type of slow‐release progesterone micro‐particles useable in a single intramuscular injection for estrus synchronization in non‐breeding season ewes. A total of 66 ewes were randomly assigned into four groups: CIDR (n = 16): exposed to intravaginal CIDR for 12 days, and three experimental groups, i.e., T100 (n = 16), T150 (n = 17) and T200 (n = 17), receiving a single intramuscular injection of 100, 150 and 200 mg slow‐release progesterone, respectively. Blood sampling was performed on all ewes at five different times, and the ELISA method measured progesterone levels. No significant differences were observed in progesterone levels among the groups in each sampling time. More than 90% of ewes in the CIDR, T100 and T150 groups and all those in T200 showed estrus behaviour, and the rate was not significantly different between groups. The difference in the mean interval from progesterone treatment to estrus was also insignificant. The parturition rate declined by increasing the dose of injected progesterone; although it was similar in CIDR and T100 groups, it decreased significantly in T150 and T200. Since our injectable progesterone formulation was successful in the induction and synchronization of estrus in ewes out of the breeding season, it can be applied as an alternative to the conventional progesterone containing intravaginal devices. [ABSTRACT FROM AUTHOR]

Curcumin (Cur) is a polyphenol compound with antioxidant and apoptotic effects. It can lead cells to death which is the ultimate goal in cancer research. The effect of Cur on three pro-apoptotic factors of Bad, Bak, and Bim was investigated in this molecular dynamic and molecular docking simulation study. The PDB files of these three factors and the 3-D structure of Cur were obtained from www.rcsb.org and PubChem, respectively. All files were converted to PDB files by Avogadro v.1.2 software. The water and ion environment in GROMACS 2018 simulation package was used to conduct molecular dynamic simulation studies. Furthermore, AutoDock v.4.2.6 software performed the docking of Cur as a ligand and the proteins as receptors. LigPlot+ v.4.5.3 was used to determine the hydrogen and hydrophobic bonds at the binding sites. Results showed that Cur could bind to Bad with -6.58 kcal/mol binding energy. In addition, the binding of Cur to proteins induced some changes in molecular dynamic factors such as radius of gyration (Rg), root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), binding energy (BE), estimated inhibition constant (EIC), and their secondary structures. A significant increase in Rg and RMSD and some variations in RMSF were seen in Bad and Bak after docking with Cur. Considering this study, Cur could bind to the proteins directly, induce conformational changes, and increase their likelihood of dimerization, leading to activating apoptotic pathways. These results suggested the apoptotic effects of Cur on cancer cells through influencing these proteins for the first time. [ABSTRACT FROM AUTHOR]

Background: Combination therapy has been one of the most pioneering and strategic approaches implemented for malignancy treatment, which can intentionally influence multiple signaling pathways involved in cancer growth and progression. In the present study, the effects of 5-fluorouracil (5FU) in combination with everolimus (EVE) or lithium chloride (LiCl) were evaluated in 4T1 metastatic breast cancer cells and compared to control and each other. Methods and results: The resazurin assay, CompuSyn, flow cytometry, and real-time PCR were used to investigate cell proliferation, drug synergism, apoptosis, and gene expression. In comparison to the ternary combination of the drugs, the findings showed that cytotoxicity (p-value < 0.0001) and apoptosis (p-value < 0.0001) of two-by-two combinations increased dramatically as a consequence of the extreme synergy between 5FU and EVE or LiCl. Moreover, the hypoxiainducible transcription factor 1-alpha (HIF-1α) and the vascular endothelial growth factor (VEGF) downregulated considerably compared to control (p-value < 0.0001) by combination therapies of EVE-5FU and 5FU-LiCl; however, only VEGF displayed significant downregulation in comparison to single therapies. Conclusion: The findings showed that the combination of 5FU-LiCl increased cell cytotoxicity and apoptosis significantly more than EVE-5FU but suggests a clinical potential for both to treat metastatic breast cancer encouraging validation of these results in pre-clinical models. [ABSTRACT FROM AUTHOR]

Aims: A controlled release drug delivery system loaded with buprenorphine and ketorolac was synthesized and used in the experimental model of bone defect and while evaluating the inflammatory response, the repair process in the defects was investigated. Materials and methods: To determine the effectiveness of the synthesized the mentioned systems, 5 groups were defined; the control group, the chitosan hydrogel receiving group (chitosan group), the ketorolac-loaded chitosan hydrogel group (ketorolac group), the buprenorphine-loaded chitosan hydrogel receiving group (buprenorphine group), and the chitosan hydrogel-loading group loaded with a combination of ketorolac and buprenorphine (ketorolac-buprenorphine group). Results: The results showed that the population of leukocytes (tWBC) and neutrophils on different days of the study in the control group compared to other groups had a significant increase (P < 0.05) while on day 7 of the study in the ketorolac group these parameters decreased significantly compared to other groups (P < 0.05). While examining the histological changes in the experimental defect created in the proximal tibia of rats at different times, some inflammatory indices such as total and differential leukocyte population, plasma concentrations of TNF-α and IL-6 were compared in different groups (P < 0.05). The various evaluated data showed that among the different groups, in the control and ketorolac-buprenorphine groups, there was the lowest and highest control of inflammatory response and bone repair, respectively. Conclusion: In the ketorolac group due to the impact of ketorolac on leukocyte populations the best bone healing can be expected among the different treatment groups. [ABSTRACT FROM AUTHOR]

Introduction: Iranian traditional medicine has recommended the use of smoke from complete burning of jennet feces as a strong anti-inflammatory and wound healing component. Therefore, the present study was done to set up an animal model of cervicitis and production of vaginal cream of this smoke to evaluate anti-inflammatory effects of that in cervicitis. Materials and Methods: We used 20 female vistar rats weighting 200-250 gr in 4 groups for animal model set up using different dosage of phenol and CMC for the first time. The vaginal cream was containing 5% jennet faces smoke. Groups were divided in to health, cervicitis model, control (receive base cream) and treatment (receive smoke cream). After induction of cervicitis, control and treatment groups were received base cream and 5% vaginal smoke cream respectively for five days. Vaginal pH was measured during of study. After 5 days, the cervix organs were examined by histopathological assay. Result: No significant difference in vaginal pH in all of 4 groups of the intervention. In the model and control groups, we observed inflammatory cell infiltration and some visible epithelial erosion. After treatment with 5% vaginal smoke cream, the pathological features of cervicitis decreased significantly; inflammation (p = 0.011), vascular congestion (p = 0.001) and erosion scores (p> 0.005). Conclusion: The smoke of jennet feces has anti-inflammatory effects on phenol-CMC induced cervicitis in rat model. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this work, large pore size MSNs were prepared by the co-condensation method. Tioguanine (TG) as a hydrophobic drug was loaded into the synthesized MSNs to prepare TG@MSNs. The results show MSNs were successfully synthesized and they have good loading efficiency and capacity for TG. Silk fibroin (SF) as an active targeting agent and pH-sensitive targeting release, is a natural protein from silkworm cocoons. It was used to coating MSNs to prepare SF/TG@MSNs. SF was Degummed and it was characterized by nuclear magnetic resonance (NMR), fourier transform infrared (FTIR) and field emission scanning electron microscopy (FESEM) methods. The MSNs were fully characterized by FESEM, transmission electron microscopy (TEM), zeta potential analysis, dynamic light scattering (DLS), nitrogen adsorption/desorption analysis, thermogravimetric analysis (TGA), X-ray diffraction (XRD) analysis, FTIR and UV-visible spectroscopies. The mechanism of TG release from SF/TG@MSNs were pH-sensitive. The in vitro release modeling revealed that TG released via the Higuchi model with fickian diffusion mechanism. In conclusion, SF/TG@MSNs exhibited a well synthesized and good payload for use in targeted drug delivery for leukemia. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for more efficient drug delivery. In this study, the efficacy of metronidazole-loaded mesoporous silica nanoparticles (MSNs/MTZ) with a pH-sensitive release against Trichomonas vaginalis trophozoites was investigated. MSNs were prepared by the sol-gel method and final particles were characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Brunauer Emmett Teller (BET), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray Diffraction (XRD) methods. MSNs were loaded with metronidazole (MTZ) to MSNs/MTZ preparation. In vitro susceptibility assay of MTZ/MSNs in Trichomonas vaginalis trophozoites was done to obtain inhibitory concentration (IC50). SEM results show particles with an approximate size of 50 nm and XRD results prove the crystalline structure of MSNs. The BET results show that pore size and surface area of these particles are 2.8 nm and 800 m2/g respectively. Other FTIR results confirm the chemical structure of the nanoparticles. The loading capacity of MSNs was 33% and the release of MTZ from the nanoparticles affected by the pH. Toxicity assay results on Trichomonas vaginalis trophozoites show increased cytotoxicity in MSNs-MTZ compared to free MTZ, whereas this evaluation confirmed that MSNs toxicity was insignificant. According to the results, it can be said that the use of MSNs is a good option for drug delivery to Trichomonas vaginalis trophozoites, and the use of these nanoparticles make MTZ more effective and performable. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer. [ABSTRACT FROM AUTHOR]