Histomorphometric analysis of goat uterine tissue on in vitro exposure with ovarian hormones and mifepristone

Uterus, the largest reproductive tract organ in female mammals, is the site of implantation of fertilised egg and foetus development. Uterus is a dynamic reproductive organ; its morphology alters with reproductive phase and steroidal cues. The aim of the present study was to assess the effects of progesterone (P4), estrogen (E2) and antiprogestogen i.e., mifepristone on goat’s uterine histoarchitecture in in vitro short term culture. Uterine tissue slices were cultured in the presence of E2, P4 and mifepristone at the dose of 10–9 M, 10–7 M and 10–6 M respectively for 24 hours. Uter-ine morphology of E2- and P4-treated groups did not reveal marked changes from that of control group. Mifepristone treatment caused conspicuous changes in uterine histoarchitecture, led to congested endometrium, regressed uterine glands and constricted blood vessels. The changes ob-served in morphometry after E2 and P4 exposure included increased uterine gland diameter (47.00 and 45.95 µm respectively) and glandular epithelial cell height (18.37 and 17.43 µm respectively) while the mifepristone treatment resulted in significant reduction of gland diameter (34.95 µm) as well as epithelium height (14.25 µm) as compared to those in control group (39.9 and 15.56 µm respectively). These morphometrical changes revealed prominent regressive changes in anti-progestin treated group while E2 and P4 showed prolific effects in in vitro culture. Thus it is envis-aged that E2 and P4 induced characteristic progressive changes in the histologic structure especially in endometrial glands of the goat uterus while anti-steroidogenic formulation i.e. mifepristone severely reduced the normal histoarchitecture of the uterus which is a prerequisite for implanta-tion.

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Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

The International Journal of Lower Extremity Wounds ◽

10.1177/15347346211002144 ◽

2021 ◽

pp. 153473462110021

Author(s):

Joon M. Jung ◽

Hae K. Yoon ◽

Chang J. Jung ◽

Soo Y. Jo ◽

Sang G. Hwang ◽

...

Keyword(s):

Wound Healing ◽

Plasma Treatment ◽

Cold Plasma ◽

Smooth Muscle Actin ◽

Treated Group ◽

Control Group ◽

Alpha Smooth Muscle Actin ◽

Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

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Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models

Cancer & Metabolism ◽

10.1186/s40170-021-00249-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Malinee Thanee ◽

Sureerat Padthaisong ◽

Manida Suksawat ◽

Hasaya Dokduang ◽

Jutarop Phetcharaburanin ◽

...

Keyword(s):

Redox Regulation ◽

Treated Group ◽

Control Group ◽

High Recurrence Rate ◽

Nucleic Acid Metabolism ◽

In Vivo Models ◽

Tryptophan Degradation ◽

Xenograft Mice

Abstract Background Sulfasalazine (SSZ) is widely known as an xCT inhibitor suppressing CD44v9-expressed cancer stem-like cells (CSCs) being related to redox regulation. Cholangiocarcinoma (CCA) has a high recurrence rate and no effective chemotherapy. A recent report revealed high levels of CD44v9-positive cells in CCA patients. Therefore, a combination of drugs could prove a suitable strategy for CCA treatment via individual metabolic profiling. Methods We examined the effect of xCT-targeted CD44v9-CSCs using sulfasalazine combined with cisplatin (CIS) or gemcitabine in CCA in vitro and in vivo models and did NMR-based metabolomics analysis of xenograft mice tumor tissues. Results Our findings suggest that combined SSZ and CIS leads to a higher inhibition of cell proliferation and induction of cell death than CIS alone in both in vitro and in vivo models. Xenograft mice showed that the CD44v9-CSC marker and CK-19-CCA proliferative marker were reduced in the combination treatment. Interestingly, different metabolic signatures and significant metabolites were observed in the drug-treated group compared with the control group that revealed the cancer suppression mechanisms. Conclusions SSZ could improve CCA therapy by sensitization to CIS through killing CD44v9-positive cells and modifying the metabolic pathways, in particular tryptophan degradation (i.e., kynurenine pathway, serotonin pathway) and nucleic acid metabolism.

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Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽

10.3390/molecules26020331 ◽

2021 ◽

Vol 26 (2) ◽

pp. 331

Author(s):

Jung-Yun Lee ◽

Tae Yang Kim ◽

Hanna Kang ◽

Jungbae Oh ◽

Joo Woong Park ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Density Lipoprotein ◽

Treated Group ◽

Control Group ◽

Chitosan Oligosaccharide ◽

Sd Rats ◽

Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

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Malondialdehyde Level in Seminal Plasma of Cryopreserved Holstein Bull Semen after Addition of Zinc, Cysteine, Prostaglandin F2α and their Combination in vitro

Al-Anbar Journal of Veterinary Sciences ◽

10.37940/ajvs.2020.13.1.12 ◽

2020 ◽

Vol 13 (1) ◽

pp. 97-100

Author(s):

M. R. G. Al-Dahan ◽

A. F. Majeed ◽

M. A. Abed ◽

F. Ibrahim ◽

K. J. yahya

Keyword(s):

Seminal Plasma ◽

Zinc Sulphate ◽

Prostaglandin F2α ◽

Treated Group ◽

Control Group ◽

Bull Semen ◽

Holstein Bull ◽

Holstein Bulls ◽

Combination Treated Group

The study was conducted to know the level of Malondialdehyde (MDA) in seminal plasma of cryopreserved semen of Holstein bulls after addition of zinc sulphate, cysteine, PGF2α and their combination in vitro. Semen was collected from 7 Holstein bulls, presented in Artificial insemination Center which belonged to the Directorate of Animal Resources/ Ministry of Agriculture at Abu-Graib at the west of Baghdad. Pooled semen were diluted with Tris- based extender and divided into five parts. The first part (T1) serve as a control (without addition). The 2nd part (T2) added to it zinc sulphate (0,576 mmol/ ml). The 3rd part (T3) added to it cysteine (5 mmol/ ml). The 4th part (T4) added to it PGF2α (37.5 pg/ ml). while the 5th part added to it a combination of previous substances at the same concentration. They packed in straws and cryopreserved in a liquid nitrogen and after 30, 60 and 90 days. Seminal plasma when isolated to measure the level of MDA. The results showed a significant decrease (P>0.01) in MDA level in the combination treated group (zinc, cysteine and PGF2α) 0.450 ± 0.11 (mmol/ ml) as compared with control group 1.025 ± 0.38 (mmol/ ml), zinc 0.867 ± 0.12 (mmol/ ml), cysteine 1.06 ± 0.12 (mmol/ ml) and PGF2α group 0.968 ± 0.17 (mmol/ ml) respectively. It was concluded from this study that addition of a combination of zinc, cysteine and PGF2α to the Holstein bull semen could decrease the level of MDA which might be due to the synergistic effect of these substances.

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Improvement of quality of oocytes collected in the autumn by enhanced removal of impaired follicles from previously heat-stressed cows

Reproduction ◽

10.1530/rep.0.1220737 ◽

2001 ◽

pp. 737-744 ◽

Cited By ~ 126

Author(s):

Z Roth ◽

A Arav ◽

A Bor ◽

Y Zeron ◽

R Braw-Tal ◽

...

Keyword(s):

Heat Stress ◽

Embryo Development ◽

Treated Group ◽

Oocyte Quality ◽

Control Group ◽

Delayed Effect ◽

Cleavage Rate ◽

Lactating Cows ◽

Summer Heat

The fertility of dairy cows decreases during the summer and remains low during the cooler autumn although the animals are no longer under heat stress. The aim of this study was to characterize a delayed effect of summer heat stress on oocyte quality in the autumn and to improve oocyte quality by enhanced removal of follicles damaged during the previous summer. Lactating cows (n = 16) were subjected to heat stress during the summer. In autumn, ovarian follicles (3-7 mm in diameter) were aspirated by an ultrasound-guided procedure during four consecutive oestrous cycles. Follicles were aspirated from control cows on day 4 and from treated cows on days 4, 7, 11 and 15 of each oestrous cycle. All cows received PGF(2alpha) and GnRH injections on days 19 and 21, respectively, and maintained cyclicity, as indicated by plasma progesterone concentrations. On day 4 of each cycle, the oocytes recovered were examined morphologically, matured and activated in vitro, and cultured for 8 days. In cycle 1 (early October) both groups showed low percentages of grade 1 oocytes, cleavage, four- and eight-cell embryos, morulae and parthenogenetic blastocysts. Subsequently, the number of grade 1 oocytes increased earlier (cycle 2) in treated than in control cows (cycle 3; P < 0.05). The cleavage rate in the control group remained relatively low throughout (32-58%), whereas in the treated group it increased from 40% (cycle 1) to 75% (cycles 3 and 4; P < 0.05). The number at each stage of embryo development increased slightly but remained low throughout in the control group, whereas in the treated group significant (P < 0.05) increases of all stages were observed in cycles 3 and 4. The results show a delayed effect of summer heat stress on oocyte quality and embryo development in the autumn. Enhanced removal of the impaired cohort of follicles led to earlier emergence of healthy follicles and high quality oocytes in the autumn.

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In Vivo Antiviral Effects of U18666A Against Type I Feline Infectious Peritonitis Virus

Pathogens ◽

10.3390/pathogens9010067 ◽

2020 ◽

Vol 9 (1) ◽

pp. 67 ◽

Cited By ~ 5

Author(s):

Tomoyoshi Doki ◽

Tomoyo Tarusawa ◽

Tsutomu Hohdatsu ◽

Tomomi Takano

Keyword(s):

Clinical Symptoms ◽

Treated Group ◽

Control Group ◽

Type I ◽

Feline Infectious Peritonitis Virus ◽

Feline Infectious Peritonitis ◽

Amphiphilic Drug ◽

Antiviral Effects

Background: The cationic amphiphilic drug U18666A inhibits the proliferation of type I FIPV in vitro. In this study, we evaluated the in vivo antiviral effects of U18666A by administering it to SPF cats challenged with type I FIPV. Methods: Ten SPF cats were randomly assigned to two experimental groups. FIPV KU-2 were inoculated intraperitoneally to cats. The control group was administered PBS, and the U18666A-treated group was administered U18666A subcutaneously at 2.5 mg/kg on day 0, and 1.25 mg/kg on days 2 and 4 after viral inoculation. Results: Two of the five control cats administered PBS alone developed FIP. Four of the five cats administered U18666A developed no signs of FIP. One cat that temporarily developed fever, had no other clinical symptoms, and no gross lesion was noted on an autopsy after the end of the experiment. The FIPV gene was detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A. Conclusions: When U18666A was administered to cats experimentally infected with type I FIPV, the development of FIP might be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats.

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Influence of Fullerenol C60(OH)24 on Doxorubicin Induced Cardiotoxicity in Rats

Materials Science Forum ◽

10.4028/www.scientific.net/msf.518.525 ◽

2006 ◽

Vol 518 ◽

pp. 525-530 ◽

Cited By ~ 17

Author(s):

V. Djordjević-Milić ◽

A. Djordjević ◽

S. Dobrić ◽

Rade Injac ◽

D. Vučković ◽

...

Keyword(s):

Structural Damage ◽

Heart Function ◽

Treated Group ◽

Heart Tissue ◽

Cardiovascular Reflexes ◽

Control Group ◽

Heart Damage ◽

Cardioprotective Effects ◽

Doxorubicin Administration

Earlier investigation of fullerenol, C60(OH)24, features, in vitro, showed that fullerenol have strong antioxidative potential. In this work, we examined the influence of fullerenol as a potential antioxidative protector on doxorubicin induced cardiotoxicity in rats. Experiments were performed on adult Wistar rats, both gender. Animals were divided into six groups, each containing eight individuals. Doxorubicin was administrated i.v. (tail vein) in single dose of 8mg/kg. Fullerenol C60(OH)24 in treated animals was administrated i.p. (in doses 50, 100, 200 mg/kg) for 30 min. before application of doxorubicin. Control group (intact animals) was given saline (1 mL/kg). One group was treated only with fullerenol (100 mg/kg i.p.). Cardiotoxicity of doxorubicin as well as cardioprotective effects of fullerenol were evaluated following the heart function monitored by ECG recording during adrenalin i.v. infusion, and pathomorphological examination of the heart tissue. These evaluations were performed on the day 2 and 7 after doxorubicin administration. Both functional and pathomorphological investigations revealed no heart damage two days after given treatments. However, on the day 7 after doxorubicin injection, changes in cardiovascular reflexes to adrenalin as well as structural damage were manifest. The time for appearance of adrenalin-induced reflex bradicardia in ECG record was significantly longer in doxorubicin treated group in comparison with the control one. Also, pathomorphological examination of the heart tissue showed vacuolization of cardiomyocites. In fullerenol pretreated groups these described changes were ameliorated and corresponded to the control values. These results suggest that fullerenol might be potential cardioprotector in doxorubicin treated individuals.

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268 ROLE OF ATPase MOTOR CYTOPLASMIC DYNEIN AND PRIMARY CILIA IN TESTICULAR MORPHOGENESIS

Reproduction Fertility and Development ◽

10.1071/rdv27n1ab268 ◽

2015 ◽

Vol 27 (1) ◽

pp. 223

Author(s):

C. Dores ◽

I. Dobrinski

Keyword(s):

Primary Cilia ◽

Somatic Cells ◽

Treated Group ◽

Cytoplasmic Dynein ◽

Control Group ◽

Tubule Formation ◽

Serum Free ◽

Free Media

In vertebrates, the primary cilium is a nearly ubiquitous organelle present in somatic cells, but little is known about its function in the male gonad. We investigated the role of primary cilia in testis cells using in vitro formation of seminiferous tubules and in vitro culture of testicular somatic cells by inhibiting the primary cilium with CiliobrevinD, a cell-permeable, reversible chemical modulator that inhibits the major component of the organelle: ATPase motor cytoplasmic dynein. We analysed in vitro cultures for the presence of primary cilia and the activation of hedgehog signalling through translocation of Gli2 to the nuclei; in vitro tubule formation was evaluated by length and width of tubules formed. Methods: testicular cells were harvested from neonatal pigs by 2-step enzymatic digestion. Cells (50 × 106 mL–1) were plated on 100 mm Petri dishes in 15 mL of DMEM + 5% FBS + 50 U of penicillin and incubated at 37°C in 5% CO2 in air overnight, cells remaining in suspension and those slightly attached were removed and the somatic cells attached were trypsinized to obtain a single cell suspension, and then submitted to two different protocols: in vitro culture (A) or in vitro tubule formation (B), n = 5 replicates each. For A, somatic cells were replated on coverslips in 24-well plates and cultured in serum free media for 48 h, then for the treated group, 10 mM of CiliobrevinD was added for 24 h, attached cells from control and treated groups were fixed in 4% PFA and characterised by immunocytochemistry for ARL13B, Vimentin, and Gli2. For B: 1 × 106 cells were added to 24-well plates coated with 1 : 1 diluted Matrigel, the control group was kept in serum free media and to the treated group was added 20 mM CiliobrevinD at Day 0. Results: A) primary cilia were present in 89.3 ± 2.3% of cells cultured in serum-free media for the control group and Gli2 was located in the nuclei of 90.2 ± 1.2% of cells; in the CiliobrevinD-treated group the percentage of primary cilia decreased (P < 0.05) to 3.1 ± 2.5% and nuclear Gli2 to 3.9 ± 0.7; B) tubules formed in the control group were significantly longer and wider than the ones formed when CiliobrevinD was added (9.91 ± 0.35 v. 5.540 ± 1.08 mm and 339.8 ± 55.78 v. 127.2 ± 11.9 µm, respectively, P < 0.05 by Student's t-test). In conclusion, the inhibition of ATPase motor cytoplasmic dynein perturbs formation of primary cilia in testicular somatic cells, blocks Hedgehog signalling, and impairs in vitro tubule formation. Therefore, primary cilia on testicular somatic cells appear to be essential for testicular morphogenesis.Research was supported by 5 R01 OD016575-13.

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Supplementation of kaempferol to in vitro maturation medium regulates oxidative stress and enhances subsequent embryonic development in vitro

Zygote ◽

10.1017/s0967199419000674 ◽

2019 ◽

Vol 28 (1) ◽

pp. 59-64

Author(s):

Yuhan Zhao ◽

Yongnan Xu ◽

Yinghua Li ◽

Qingguo Jin ◽

Jingyu Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Caspase 3 ◽

Treated Group ◽

Control Group ◽

Oxygen Species

SummaryKaempferol (KAE) is one of the most common dietary flavonols possessing biological activities such as anticancer, anti-inflammatory and antioxidant effects. Although previous studies have reported the biological activity of KAE on a variety of cells, it is not clear whether KAE plays a similar role in oocyte and embryo in vitro culture systems. This study investigated the effect of KAE addition to in vitro maturation on the antioxidant capacity of embryos in porcine oocytes after parthenogenetic activation. The effects of kaempferol on oocyte quality in porcine oocytes were studied based on the expression of related genes, reactive oxygen species, glutathione and mitochondrial membrane potential as criteria. The rate of blastocyst formation was significantly higher in oocytes treated with 0.1 µm KAE than in control oocytes. The mRNA level of the apoptosis-related gene Caspase-3 was significantly lower in the blastocysts derived from KAE-treated oocytes than in the control group and the mRNA expression of the embryo development-related genes COX2 and SOX2 was significantly increased in the KAE-treated group compared with that in the control group. Furthermore, the level of intracellular reactive oxygen species was significantly decreased and that of glutathione was significantly increased after KAE treatment. Mitochondrial membrane potential (ΔΨm) was increased and the activity of Caspase-3 was significantly decreased in the KAE-treated group compared with that in the control group. Taken together, these results suggested that KAE is beneficial for the improvement of embryo development by inhibiting oxidative stress in porcine oocytes.

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Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

Bioscience Reports ◽

10.1042/bsr20160234 ◽

2016 ◽

Vol 36 (5) ◽

Cited By ~ 5

Author(s):

Jiang-Ying Ru ◽

Hai-Dong Xu ◽

Dai Shi ◽

Jun-Bo Pan ◽

Xiao-Jin Pan ◽

...

Keyword(s):

Cathepsin K ◽

Treated Group ◽

Receptor Activation ◽

Raw264.7 Cells ◽

Control Group ◽

Nuclear Factor ◽

Trabecular Thickness ◽

Tnf Α

Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied and classical endotoxin produced by Gram-negative bacteria, act to increase the biological activity of osteopedic wear particles such as polymethyl-methacrylate (PMMA) and titanium particles in cell culture and animal models of implant loosening. The present study was designed to explore the inhibitory effect of UTI on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 cells and murine osteolysis models, and investigate the potential mechanism. The in vitro study was divided into the control group, LPS-induced group, PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of inflammatory mediators including tumour necrosis factor-α (TNF-α), matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation of nuclear factor NF-κB (RANK), and cathepsin K were examined and the amounts of phosphorylated I-κB, MEK, JNK and p38 were measured. In vivo study, murine osteolysis models were divided into the control group, PMMA-induced group and UTI-treated group. UTI (500 or 5000 units/kg per day) was injected intraperitoneally followed by PMMA suspension with adherent LPS (2×108 particles/25 μl) in the UTI-treated group. The thickness of interfacial membrane and the number of infiltrated inflammatory cells around the implants were assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over total volume (BV/TV) of distal femur around the implants were calculated. Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9, IL-6, TNF-α, RANK and cathepsin K through down-regulating the activity of nuclear factor kappa B (NF-κB) and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.

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