The analysis of boric acid effect on epithelial-mesenchymal transition of CD133 + CD117 + lung cancer stem cells.

Targeting lung cancer stem cells (LC-SCs) for metastasis may be an effective strategy against lung cancer. This study is the first on epithelial-mesenchymal transition (EMT) properties of boric acid (BA) in LC-SCs. LC-SCs were isolated using the magnetic cell sorting (MACS) method. Tumor-sphere formation and flow cytometry confirmed CSC phenotype. The cytotoxic effect of BA was measured by MTT analysis, and the effect of BA on EMT was examined by migration analysis. The expression levels of ZEB1, SNAIL1, ITGA5, CDH1, ITGB1, VIM, COL1A1, and LAMA5 genes were analyzed by RT-qPCR. E-cadherin, Collagen-1, MMP-3, and Vimentin expressions were analyzed immunohistochemically. Boric acid slightly reduced the migration of cancer cells. Increased expression of transcription factor SNAIL (p < 0.001), but not ZEB1, was observed in LC-SCs. mRNA expression levels of ITGB1 (p < 0.01), ITGA5 (p < 0.001), COL1A1 (p < 0.001), and LAMA5 (p < 0.001) increased; CDH1 and VIM decreased in LC-SCs. Moreover, while E-cadherin (p < 0.001) and Collagen-1 (p < 0.01) immunoreactivities significantly increased, MMP-3 (p < 0.001) and Vimentin (p < 0.01) immunoreactivities decreased in BA-treated LC-SCs. To conclude, the current study provided insights into the efficacy and effects of BA against LC-SCs regarding proliferation, EMT, and cell death for future studies.

SPC212 human mesothelioma cells underwent apoptosis, oxidative stress, and morphological deformation following Astaxanthin treatment.

Astaxanthin (ASX) is one of the keto-carotenoids, which is biologically more active than other counterparts. Besides its variety of beneficial effects, it was reported to exert anticancer effects. Despite its utilization against different cancer types, the effect of ASX on mesothelioma has yet to be well-studied. In this study, our goal is to ascertain how ASX will affect SPC212 human mesothelioma cells. First, the effective doses of ASX against SPC212 cells were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Thereafter, with flow cytometry analysis, Annexin-V and caspase 3/7 assay were implemented for the evaluation of apoptotic cell death and an oxidative stress test was carried out to determine how the free radicals changed. Ultimately, the cells' morphology was examined under a light microscope. The effective doses of ASX were found as 50, 100, and 200 µM. In the Annexin V assay, the total apoptosis increased to around 12%, 30%, and 45% with increasing doses of ASX. In the caspase 3/7 assay, the total apoptosis was around 25% and 38% at 100 and 200 µM. In oxidative stress analysis, reactive oxygen species-positive cells rose from 4.54 at the lowest dose to 86.95 at the highest dose. In morphological analysis, cellular shrinkage, decrease in cell density, swelling and vacuolations in some cells, membrane blebbing, and apoptotic bodies are observed in ASX-treated cells. To conclude, the current study provided insights into the efficacy and effects of ASX against SPC212 mesothelioma cells regarding morphology, proliferation, and cell death for future studies.

Does the use of antibiotic spacer disrupt induced membrane function?

Treatment of large segmental bone defects has been a challenging and long process for both physicians and patients. At present, the induced membrane technique is one of the reconstruction techniques commonly utilized in treating large segmental bone defects. It consists of a two-step procedure. In the first one, after bone debridement, the defect is filled with bone cement. The aim at this stage is to support and protect the defective area with cement. A membrane is formed around the area where cement was inserted 4-6 weeks after the first surgical stage. This membrane secretes vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), as shown in the earliest studies. In the second step, the bone cement is removed, and the defect is filled with cancellous bone autograft. In the first stage, antibiotics can be added to the applied bone cement, depending on the infection. Still, the histological and micromolecular effects of the added antibiotic on the membrane are unknown.This study investigates the molecular and histological effects of antibiotics addition into bone cement on the induced membrane.In this study, conducted on 27 male New Zealand rabbits, the 2 cm long defects of a bone were created in the rabbit femurs. Three groups were formed by placing antibiotic-free, gentamicin, and vancomycin-containing cement in the defect area.These groups were followed for six weeks, and the membrane formed at the end of 6 weeks was examined histologically. As a result of this study, it found that the membrane quality markers (Von Willebrand factor (vwf), Interleukin 6-8 (IL), Transforming growth factor beta (TGF-ß), Vascular endothelial growth factor (VEGF) were significantly higher in the antibiotic-free bone cement group. Our study has shown that antibiotics added to the cement have negative effects on the membrane. Based on the results we obtained, it would be a better choice to use antibiotic-free cement in aseptic nonunions. However, more data is needed to understand the effects of these changes on the cement on the membrane.

Beta-carotene exerted anti-proliferative and apoptotic effect on malignant mesothelioma cells.

High blood levels of ß-carotene and increased intake in the diets are inversely proportional to incidence of many cancer types. Antioxidant activity of ß-carotene was proposed to be related with its antitumor effect. Despite this plant derivative substance being sought in many cancer types, the effectiveness of ß-carotene against malignant mesothelioma remained unclear. Therefore, the present study aims to explore the impact of ß-carotene on cell viability, apoptosis, and oxidative stress in mesothelioma cells. Human mesothelioma cell SPC212 were treated with ß-carotene (3.125-200 µM) for 24, 48, 72, and 96 h. Cytotoxicity was measured with the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Annexin-V/propidium iodide (PI) and caspase 3/7 biomarkers were used to identify apoptotic cells. Finally, the oxidative stress was evaluated with flow cytometry. The results of the measurements indicated a significant decline in viable mesothelioma cancer cell numbers upon ß-carotene treatment in time- and concentration-dependent manner when compared to control cells. Furthermore, ß-carotene treatment led to apoptosis induction according to both annexin V/PI and caspase 3/7 assays. Furthermore, ß-carotene increased oxidative stress in SPC212 cells. These results show how ß-carotene affects proliferative, apoptotic, and oxidative properties in SPC212 malignant pleural mesothelioma cells and provide useful insights into future studies.

The effects of thymoquinone and quercetin on the toxicity of acrylamide in rat glioma cells.

Acrylamide is a neurotoxic agent forming in foods. Thymoquinone and quercetin are plant-derived antioxidants in various foods with known benefits. C6 cells are glioblastoma cells. In this study, we aimed at preventing acrylamide toxicity by thymoquinone and quercetin in the C6 cell line. In our study, first, toxic doses of acrylamide, nontoxic doses of thymoquinone and quercetin in C6 cells for 24 h were determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric test. After that, caspase 3/7 and annexin V tests were performed by flow cytometry to evaluate whether the apoptosis pathway was inducted. Furthermore, autophagy and oxidative stress were assessed by flow cytometry. The amount of Nrf2 (nuclear factor erythroid 2-related factor 2) was determined by immunocytochemistry. The morphological examination was performed by microscopic analyses. As a result, 4 mM of acrylamide was determined to be used to induce toxicity in C6 cells. The nontoxic doses of thymoquinone and quercetin were respectively determined as 3.9 and 2.0 µM. Thymoquinone and quercetin not only reduced acrylamide-induced apoptosis in annexin V and caspase 3/7 assays but also morphological deformations in microscopic examinations. In autophagy, it was revealed that acrylamide-induced autophagy was decreased by quercetin and thymoquinone pretreatments. As for Nrf2 expression, it was observed that acrylamide increased Nrf2 expression, and thymoquinone and quercetin pretreatments increased it even further. In conclusion, in the study, acrylamide demonstrated a damaging effect on C6 glioblastoma cells, and thymoquinone and quercetin pretreatments exerted a protective effect against acrylamide-induced damage in C6 cells.

Investigation into the protective effects of Hypericum Triquetrifolium Turra seed against cyclophosphamide-induced testicular injury in Sprague Dawley rats.

For centuries, Turkey has been a significant location here around 80 species of Hypericum with differing names widely occur, which is also known as Turkish folk medicine in treating some bacterial diseases as well as stomach and intestine inflammation. Recent studies have reported this herb family to contain numbers of bioactive compound contents. The study aims to investigate the protective effects of Hypericum triquetrifolium Turra (HT) upon oxidative stress and apoptosis in a rat model in which testes injury was induced by CP. The testicular injury was caused using CP (150 mg/kg). The rats were treated with a single dose (100 mg/kg) of methanol extract of HT to investigate various biochemical markers in the serum and plasma of blood samples apart from assessing the prognosis of CP-induced testicular damage. Added to that, histological analyses were performed to identify possible structural changes and apoptotic indicators, like Bax, Caspase-3, and Bcl-2. In CP Group, there was a rise in the levels of total oxidant status (TOS), malondialdehyde (MDA), oxidative stress index (OSI), Caspase-3, and Bax while superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), Bcl-2, and total antioxidant capacity (TAC) all decreased. Also, our histological analysis showed damaged testes. On the other hand, neither biochemical nor histological analysis showed testicular damage in HT Alone Group. In CP + HT Group, a significant number of the negatives changes due to CP were observed to have improved remarkably following an HT treatment. This study results suggest that HT could help improve CP-induced testicular injury thanks to its anti-oxidative and anti-apoptotic properties.

Effects of metformin on lipopolysaccharide induced inflammation by activating fibroblast growth factor 21.

Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria that produces endotoxemia, which may cause septic shock. Metformin (MET) is a widely used hypoglycemic drug that exhibits anti-inflammatory properties. Fibroblast growth factor 21 (FGF21) is an endocrine polypeptide that affects glucose and lipid metabolism, and also possesses anti-inflammatory properties. We investigated the effects of MET and FGF21 on inflammation due to LPS induced endotoxemia in male rats. Animals were divided into five groups: control, LPS, pre-MET LPS, LPS + 1 h MET and LPS + 3 h MET. Serum levels of alanine aminotransferase, aspartate aminotransferase, FGF2, interleukin-10 and tumor necrosis factor alpha were measured. Malondialdehyde, myeloperoxidase and FGF21 levels were measured in liver tissue samples. Histopathology of all groups was assessed using hematoxylin and eosin stained sections. LPS caused severe inflammatory liver damage. MET exhibited a partially protective effect and reduced inflammation significantly. FGF21 is produced in the liver following inflammation and MET may increase its production.

ß-Hydroxybutyrate, One of the Three Main Ketone Bodies, Ameliorates Acute Pancreatitis in Rats by Suppressing the NLRP3 Inflammasome Pathway.

BACKGROUND: Acute pancreatitis (AP) is a widespread disease resulting from the inflammation of acinar cells in the pancreas. ß-hydroxybutyrate (BHB) is a water-soluble main ketone body synthesized in the human liver. The purpose of this study was to examine the possible therapeutic effects of BHB in the experimentally-induced AP model in rats. METHODS: In our study, male rats were randomly allotted into 6 groups, as control (0.9% saline i.p.), BHB1 (200 mg/kg BHB i.p.), BHB2 (2 doses of 200 mg/kg BHB i.p.), AP (4 doses of 50 µg/kg cerulein i.p., 4 doses at 1 h intervals), AP+BHB1 and AP+BHB2 groups. In pancreatic tissue sections, immunohistochemistry staining and western blot analysis for the inflammasome complex (caspase-1, ASC, and NLRP3) and inflammation-associated proteins (TNF-α and NF-κB) and a histopathological examination were performed. The levels of lipase, amylase, interleukin (IL)-18 and IL-1ß in serum were measured. RESULTS: Several pathological degenerations, including edema, inflammatory cell infiltration, acinus necrosis, and bleeding were observed in the AP group, while the histological architecture of the control and the sham BHB1 and BHB2 groups were regular. The AP-induced pathological changes were considerably alleviated in the AP+BHB1 and AP+BHB2 groups. In the AP group, a conspicuous increase in caspase-1, ASC, NLRP3, TNF-α, and NF-κB proteins, and in the levels of amylase, lipase, IL-18, and IL-1ß were detected. BHB treatments after AP induction decreased those proteins to the level of control. CONCLUSIONS: We demonstrated that BHB has the potential to cure AP by suppressing the NLRP3 inflammasome and can be used in the treatment of many diseases which progress through the NLRP3 inflammasome.

The Protective Agents Used against Acrylamide Toxicity: An In Vitro Cell Culture Study-Based Review.

Acrylamide is a dangerous electrophile with the potency to react with many biological moieties including proteins, and nucleic acids as well as other macromolecules. Acrylamide was first only known a chemical exposed in working areas as a neurotoxicant, it was later discovered that beyond just being a neurotoxicant exposed in industrial areas, acrylamide is exposed via daily foods as well. As such, several strategies have been sought to be developed to relieve the toxic spectrum of this chemical. The utilization of a protective agent against acrylamide toxicity was one of those strategies. To date, many agents with protective potency have been investigated. Herein, we compiled these agents and their effects shown in in vitro studies. We used the search engines of Web of Knowledge and searched the keywords "acrylamide" and "protect" in the titles along with the keyword "cell" in the topics. Twenty-one directly related articles out of 35 articles were examined. Briefly, all agents used against acrylamide were reported to exhibit protective activity. In most of these reports, 5 mM concentration of acrylamide and 24-hour treatment were the employed dose and duration. Usually, the beneficial agents were pre-treated to the cells. PC12 cells were the most utilized cell line, and the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways were the most studied pathways. This study, beside other importance, can be utilized as a guide for how the protective studies against acrylamide were done and which parameters were investigated in in vitro acrylamide studies. In conclusion, taking measures is of utmost importance to prevent or alleviate the toxicity of acrylamide, to which we are daily exposed even in our homes. Therefore, future studies should persist in focusing on mitigating acrylamide toxicity.

Cardiac hypertrophy caused by hyperthyroidism in rats: the role of ATF-6 and TRPC1 channels.

Hyperthyroidism influences the development of cardiac hypertrophy. Transient receptor potential canonical channels (TRPCs) and endoplasmic reticulum (ER) stress are regarded as critical pathways in cardiac hypertrophy. Hence, we aimed to identify the TRPCs associated with ER stress in hyperthyroidism-induced cardiac hypertrophy. Twenty adult Wistar albino male rats were used in the study. The control group was fed with standard food and tap water. The group with hyperthyroidism was also fed with standard rat food, along with tap water that contained 12 mg/L of thyroxine (T4) for 4 weeks. At the end of the fourth week, the serum-free triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) levels of the groups were measured. The left ventricle of each rat was used for histochemistry, immunohistochemistry, Western blot, total antioxidant capacity (TAC), and total oxidant status (TOS) analysis. As per our results, activating transcription factor 6 (ATF-6), inositol-requiring kinase 1 (IRE-1), and TRPC1, which play a significant role in cardiac hypertrophy caused by hyperthyroidism, showed increased activation. Moreover, TOS and serum-free T3 levels increased, while TAC and TSH levels decreased. With the help of the literature review in our study, we could, for the first time, indicate that the increased activation of ATF-6, IRE-1, and TRPC1-induced deterioration of the Ca2+ ion balance leads to hypertrophy in hyperthyroidism due to heart failure.

Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.

BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell. MATERIAL AND METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method. RESULT: 250 µM astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients. CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results. KEY WORDS: Breast, cancer, metastasis.

Investigation of the effect of hyperthyroidism on endoplasmic reticulum stress and tran- sient receptor potential canonical 1 channel in the kidney

Background/aim: Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angio- tensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are gluco- se-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1). Materials and methods: Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also im- munohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies. Results: TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analy- sis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05). Conclusion: In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.

Cyproheptadine causes apoptosis and decreases inflammation by disrupting thiol/disulfide balance and enhancing the levels of SIRT1 in C6 glioblastoma cells.

Cyproheptadine is first-generation antihistamine drug, that is, H1 receptor antagonist, with a drug being anesthetic, anti-serotonergic and anti-cholinergic and started to be used clinically in the 1960s. As firstly utilized as an anti-allergic drug, usage of cyproheptadine was expanded to other cases including serotonin syndrome, appetite increasing, migraines and insomnia. However, there are almost few studies seeking to explore the association between cyproheptadine and cancer in general. In the present study, we sought to determine the impact of cyproheptadine on C6 glioblastoma cells by morphological, biochemical and cytotoxic analyzes. We searched the effective doses of cyproheptadine for C6 glioblastoma cells and examined the cells under an inverted microscope. Next, we determined the protein levels of SIRT1, NFκB and IL-6 protein. Then, we measured and calculated the levels of thiols, disulfide bonds and related parameters. After that, we evaluated apoptotic activity by Annexin V and caspase 3 assays. As a result, we detected a dose-dependent increase in apoptosis and SIRT 1 protein levels, and a decrease in inflammatory proteins. Furthermore, we have detected a drop in thiol and disulfide content. Our study suggests that Cyproheptadine causes apoptosis and decreases inflammation by disrupting thiol/disulfide balance and enhancing the levels of SIRT1, offering the potential for being an anti-cancer drug. Therefore, it might be further investigated in future studies.

Concanavalin A induces apoptosis in a dose-dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells.

Glioma is the most common brain tumor. C6 rat glioblastoma cells provide the possibility to the scientist to study brain cancer. Concanavalin A (Con A) has a lot of antitumoral effects, especially over oxidative stress. In the present study, it was aimed to decide the impacts of various doses of Con A on C6 glioblastoma cells regarding cytotoxicity, thiol/disulfide homeostasis, apoptosis, and inflammation. We detected the cytotoxic activity of Con A (from 7.8 to 500 µg/ml) in C6 cells by utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and determined the toxic concentration of Con A. Once the optimal doses were found, the thiol-disulfide homeostasis, levels of total antioxidant and oxidant status (TAS and TOS), malondialdehyde (MDA) and glutathione (GSH), pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), apoptotic proteins as cytochrome c (CYCS), and caspase 3 (CASP3) were measured. Apoptotic and morphological changes in the C6 cells were examined with an inverted microscope and flow cytometry technique. Dose-dependent Con A triggered oxidative damage in the C6 cells, affecting the inflammatory pathway, so reducing proliferation with apoptotic proteins and morphological changes. But especially, Con A increased disulfide formation by disrupting the thiol/disulfide balance in C6 cells. This study revealed that Con A, known as carbohydrate-binding protein, generated oxidative damage, inflammation, and apoptosis in a dose-dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells.

Bexarotene inhibits cell proliferation by inducing oxidative stress, DNA damage and apoptosis via PPARγ/ NF-κB signaling pathway in C6 glioma cells.

Gliomas are one of the most aggressive brain tumors with a poor prognosis in the central nervous system. Bexarotene is a third-generation retinoid X receptor agonist that is promising in the treatment of both cancer and neurodegenerative diseases. In this study, we aimed to investigate the cytotoxic and anti-proliferative effects of bexarotene in C6 glioma cells through the PPARγ/NF-κB pathway. In the study, first cytotoxic bexarotene concentrations for C6 cells were detected, and then apoptosis profile, reactive oxygen species (ROS), total antioxidant (TAS), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear factor-κB (NF-κB) levels in the cells were determined. In addition, peroxisome proliferator-activated receptor γ (PPARγ) mRNA expression analysis was carried out. As a result, we detected concentration- and time-dependent antiproliferative effects of bexarotene on C6 cells. We found that bexarotene treatment decreased NF-κB and TAS levels and increased PPARγ and 8-OHdG levels in C6 cells. Bexarotene enhanced PPARγ expression in a dose-dependent manner when compared to the control group (P < 0.01). Furthermore, we determined that bexarotene-induced apoptotic C6 cells enhanced through Annexin V-FITC/PI staining and caspase-3/-7 activation analyses since phosphatidylserine level on the outer surface of the cell membrane and caspase-3/-7 activities were increased in the cells treated with bexarotene. In conclusion, bexarotene treatment in C6 glioma cells could modulate apoptosis profile, DNA damage, ROS production, and reduction of TAS levels through inhibition of NF-κB by enhancing PPARγ expression.

Silver ion-doped calcium phosphate-based bone-graft substitute eliminates chronic osteomyelitis: An experimental study in animals.

Despite the latest technologies and advances in microbiology and orthopedic surgery, chronic osteomyelitis is still a challenging disorder. Antibiotic resistance and bacterially induced bone destruction can have very serious consequences. We hypothesized that calcium phosphate-based bone graft substitution with silver ion doping would simultaneously treat bone infection and the bony defect in the chronic osteomyelitis. An unicortical 10-mm-diameter bone was harvested in the proximal tibial metaphysis of 24 rabbits. After contaminating the wounds with an infective dose of methicillin-resistant Staphylococcus aureus (MRSA), osteomyelitis was proven radiographically and microbiologically in all rabbits. Animals were than divided into three groups. The first group received vancomycin-impregnated bone cement beads (comparative control group), the second/experimental group received silver ion-doped calcium phosphate beads and the third group received pure calcium phosphate beads (negative controls). Radiographs, intraosseous cultures, and histopathological examinations were performed on postoperative Week 10. The cultures showed no evidence of intramedullary infection in the silver ion-doped calcium phosphate beads group, but they were positive for MRSA in four of the six rabbits in the vancomycin- impregnated bone cement beads group and in all of the eight rabbits in the pure calcium phosphate beads group. Quantitative assessment of histopathological examination showed lowest total damage score in silver ion-doped calcium phosphate beads group (p < .001). Percentage of osteoid tissue + bony tissue was also higher in this group compared with other groups. In the final radiological examinations, it was observed that the changes caused by osteomyelitis in the bone tissue in the silver ion-doped calcium phosphate beads group were much improved compared with the vancomycin-impregnated bone cement beads group. Silver ion doped calcium phosphate-based bone-graft substitute offer the ability to stimulate bone growth, combat infection, and, ultimately, treat experimental chronic osteomyelitis in an animal model.

Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: Protective role of boron.

BACKGROUND: Cyclophosphamide (CP) is an alkylating chemotherapeutic drug used in the treatment of many types of cancer. However, as with other chemotherapeutic drugs, the use of CP is limited by the damage to healthy tissues such as testes, bladder and liver as well as cancerous tissue. Boron (B) is a trace element with many biological properties such as antioxidant, anti-apoptotic and anti-lipid per oxidation. METHODS: This current study aims to determine protective effects of B on CP induced testicular toxicity. The rats were divided into 4 groups (control, CP, B and B plus CP groups). The testes of experimental animals were taken for histological, apoptotic markers and biochemical analysis. RESULTS: The damage to some seminifer tubules, loss of typical appearance, thinning of seminifer epithelium and relative enlargement of the tubule lumen were watched in testis of the group that administrated CP. Moreover, Bcl-2, TAC and GSH levels decreased while TOC, OSI, MDA, Bax and Caspase-3 levels increased. On the other hand, pretreatment limited to B in the B plus CP group, testicular tissue improved. In addition, Bcl-2, GSH, TAC levels increased, Bax, MDA, TOC, OSI and caspase-3 levels decreased. CONCLUSION: B significantly reduced testicular lipid per-oxidation and strengthened antioxidant defenses. Our results showed that pre-treatment B can protect rat testis against CP-induced testicular damage owing to its anti-lipid per oxidation, anti-oxidant and anti-apoptotic properties.

Protective effect of carnosic acid on acrylamide-induced liver toxicity in rats: Mechanistic approach over Nrf2-Keap1 pathway.

Acrylamide is a food contaminant with a range of toxic effects. Carnosic acid (C20 H28 O4 ) is a phenolic compound found in plants and has many beneficial effects. In this study, we aimed at investigating the effect of carnosic acid on acrylamide-induced liver damage. Rats (n = 7) were allotted to control, carnosic acid, acrylamide, acrylamide + carnosic acid groups. Animals were euthanized. Their blood was taken for biochemical analysis, and liver tissue was excised for morphological, immunohistochemical, and immunoblotting analyses. As a result, acrylamide reduced bodyweight, liver weight, catalase, and total antioxidant capacity levels but increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total oxidant status, oxidative stress index levels, Nrf2, and Keap1 protein levels. In addition, acrylamide disrupted liver histology leading to vascular congestion, cellular infiltration, necrotic cells, and so forth. Carnosic acid cotreatment ameliorated the altered biochemical parameters, liver histology, Nrf2, and Keap1 enzyme levels. In conclusion, carnosic acid has the potential to be used as a protective agent against acrylamide-induced liver damage.

Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice.

Nonalcoholic fatty liver disease (NAFLD) is an important health problem. The prevalence of NAFLD is increasing, especially in the Western countries. Although there are several intracellular pathways in NAFLD, endoplasmic reticulum (ER) stress has recently gained importance. Silymarin is an important liver-protective biological molecule. In light of this information, we investigated mice for the effect of silymarin on ER stress in the NAFLD model. In our study, the mice were randomly divided into six groups: Control, silymarin 100 and 200 mg/kg sham, fructose-induced NAFLD, and NAFLD + silymarin groups. After the last administrations, liver and blood samples were taken and hematoxylin-eosin, as well as Oil red O staining, were performed. As a result, the body and liver weights, lipid profile, AST, ALT, and glucose levels, along with the ER stress markers, increased in the NAFLD-only group. Silymarin treatments reversed most of these changes. Particularly, 200 mg/kg silymarin was more effective. PRACTICAL APPLICATIONS: According to the results, silymarin attenuated NAFLD by decreasing the ER stress proteins GRP78 and XBP-1. Silymarin may be therapeutic in the treatment of NAFLD as well as other ER-stress-based diseases. Silymarin can also be taken with food for prophylactic purposes.