Cyclophosphamide stimulates endoplasmic reticulum stress and induces apoptotic cell death in human glioblastoma cell lines.

Cyclophosphamide (CP) is an alkylating chemotherapeutic agent commonly used in cancer treatments. In this study, we aimed to investigate the effects of 4-Hydroperoxy cyclophosphamide (4-HC), which is active form of CP, on glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phospho-protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (p-PERK), phospho-inositol-requiring enzyme 1 alpha (p-IRE1α), eukaryotic translation initiation factor 2 alpha (eIF2α), and caspase-3 messenger ribonucleic acids (mRNAs) and proteins that play roles in the ER stress pathway and apoptosis in U87 and T98 human glioblastoma cell lines. U87 and T98 human glioblastoma cell lines were divided into control and 4-HC-treated groups. Cell viability assay was used to detect the half maximal inhibitory concentration (IC50) for 24 hours of 4-HC. Immunocytochemistry and quantitative polymerase chain reaction (qPCR) methods were used to evaluate the levels of proteins and their mRNAs. The IC50 values of U87 and T98 cells were calculated as 15.67±0.58 µM and 19.92±1 µM, respectively. The levels of GRP78, ATF6, p-PERK, p-IRE1α, eIF2α, and caspase-3 protein expressions in the 4-HC-treated group compared to that in the control group. These increased protein expressions also were correlated with the mRNA levels. The ER stress signal pathway could be active in 4-HC-induced cell death. Further studies of ER-related stress mechanisms in anticancer treatment would be important for effective therapeutic strategies.

Investigation of the Anticancer Effect of S-Allyl-L Cysteine on the C6 Rat Glioma Cell Line in vitro in 2D- and 3D-Cell Culture Models.

AIM: To investigate the antiproliferative and apoptotic effects of S-allyl cysteine (SAC) on C6 glioblastoma cells using two- and three-dimensional (2D and 3D) cell culture systems. MATERIAL AND METHODS: Three groups of rat glioma cell line C6 were prepared: 2D-Control, 2D-SAC, 3D-CMC-Control, and 3D-CMC-SAC. The control cells were incubated under standard culture conditions, the SAC cells were incubated in a culture medium supplemented with the IC50 dose (50 ?M for both the 2D-SAC C6 and 3D-CMC-SAC groups) of SAC for 24 and 48 h. All experimental cells were stained with antibodies recognizing NOTCH1 and JAGGED1, and the mRNA expression levels of NOTCH1 and JAGGED1 were evaluated by qRT-PCR. RESULTS: Increasing doses of SAC were administered for 24 h to the C6 glioma cell line. The concentration of 50 ?M was selected as the most suitable dose for administration. The gene expression profiles differed between these two cell culture types. We found that the expression levels of NOTCH1 receptor mRNA were lower in cells exposed to 50-?M SAC for 24 h than those of control cells in both 2D and 3D cell cultures. The immunoreactivities of both the biomarkers JAGGED1 and NOTCH1 in the glioma cells decreased significantly in the SAC group. CONCLUSION: These findings indicate that SAC is a potential drug candidate for human use, as indicated by its nontoxic nature. In addition, SAC was found to exert an anticancer effect, which is associated with the modulation of JAGGED1 and NOTCH1 signaling pathways in glioma cancer cells.

Understanding the role of the gut microbiome in gastrointestinal cancer: A review.

Gastrointestinal cancer represents one of the most diagnosed types of cancer. Cancer is a genetic and multifactorial disease, influenced by the host and environmental factors. It has been stated that 20% of cancer is caused by microorganisms such as Helicobacter pylori, hepatitis B and C virus, and human papillomavirus. In addition to these well-known microorganisms associated with cancer, it has been shown differences in the composition of the microbiota between healthy individuals and cancer patients. Some studies have suggested the existence of the selected microorganisms and their metabolites that can promote or inhibit tumorigenesis via some mechanisms. Recent findings have shown that gut microbiome and their metabolites can act as cancer promotors or inhibitors. It has been shown that gastrointestinal cancer can be caused by a dysregulation of the expression of non-coding RNA (ncRNA) through the gut microbiome. This review will summarize the latest reports regarding the relationship among gut microbiome, ncRNAs, and gastrointestinal cancer. The potential applications of diagnosing and cancer treatments will be discussed.

Comparison of cerebral AVMs in patients undergoing surgical resection with and without prior endovascular embolization.

AIM: Brain arteriovenous malformations (AVMs) are congenital anomalies that present as intracranial hemorrhage or epilepsy. AVMs often remain clinically silent for extended periods. Although AVM treatment methods are controversial, three treatment strategies are usually combined or applied alone: surgical removal, embolization and stereotactic radiosurgery. We compared clinical and radiological outcomes in intracranial AVM patients treated via surgical resection with and without prior embolization. MATERIALS AND METHODS: Patients who did (30 patients) and did not (30 patients) undergo endovascular embolization before surgical resection at the Izmir Katip Çelebi University Atatürk Training and Research Hospital Neurosurgery Clinic from 2011 to 2019 were included in this retrospective, cohort study. Symptoms at diagnosis, comorbidities and clinical (AVM and Spetzler-Martin grade) and morphological characteristics were assessed. RESULTS: A mean one-year follow-up assessed outcomes using the modified Rankin score, and imaging studies assessed AVM obliteration post-procedure. Mean operation times for surgical resection with and without embolization were 166.50 ± 32.02 and 204.47 ± 26.66 min, respectively. Mean patient hospitalization periods for surgical resection with and without embolization were 8.43 ± 3.60 and 12.00 ± 5.51 days, respectively. CONCLUSION: Among patients who underwent surgical resection, significant operation time and hospitalization time differences were observed in favor of patients who underwent embolization, indicating that preoperative embolization is a safe and beneficial method for treating ruptured and non-ruptured AVMs.

Research Into the Effect of Proton Pump Inhibitors on Lungs and Leukocytes.

BACKGROUND: Proton pump inhibitors (PPI) are the most commonly used medication in the world. They are prescribed as an effective treatment choice for gastrointestinal system diseases linked to hyperacidity, especially. Additionally, non-indication and unnecessary use are very common. Many publications in recent times have reported significant side effects. However, there are insufficient studies about the mechanism for these side effects. METHODS: Twenty-four Wistar albino rats were used in this study. Rats were divided into 3 groups of control, group-administered H2 receptor blockers and a group-administered PPI. Medications were administered for 30 days intraperitoneal. After 30 days, rats were euthanized and lung tissue was obtained. Lung was stained for immunohistochemical catalase, superoxide dismutase, Glutathione peroxidase, myeloperoxidase, and toluidine blue and investigated with a light microscope. Transmission electron microscopy (TEM) was used to investigate lung tissues and neutrophil leukocytes. Additionally, lung tissue had biochemical hydrogen peroxide (H2O2) levels researched. RESULTS: H2O2 amounts, produced by lysosomes with important duties for neutrophil functions in lung tissues, were found to be statistically significantly reduced in the group-administered PPI. Results from investigations of specimens obtained with immunohistochemical staining observed increases in antioxidant amounts in the PPI group. Investigation with TEM identified more inflammation findings in the lung tissue from the group-administered PPI compared to the control group and the group-administered H2 receptors. CONCLUSION: In conclusion, we identified long-term PPI use disrupts neutrophil leukocyte functions in the lung. All clinicians should be much more careful about PPI use.

Evaluation of the protective effects of non-thermal atmospheric plasma on alveolar bone loss in experimental periodontitis.

OBJECTIVES: The inhibition of bone destruction is one of the main goals of periodontitis treatment. The aim of this study was to investigate the protective effects of non-thermal atmospheric plasma (NTAP) on alveolar bone loss radiographically, histomorphometrically, and histologically in experimental periodontitis in rats. MATERIALS AND METHODS: A total of twenty-eight rats were randomly divided into three groups: control group (CG) (n = 8), periodontitis group (PG) (n = 10), and NTAP group (NTAPG) (n = 10). In PG and NTAPG, experimental periodontitis was created with ligating. The kINPen 11 plasma jet was applied around the ligatured teeth in NTAPG. The samples from each group were radiographically assessed with microcomputed tomography (micro-CT); then, histological (presence of osteoclasts and inflammatory cells) and immunohistochemical (immunoreactive of OCN and ALP) findings were compared. RESULTS: The results revealed a significant increase in alveolar bone loss in the PG compared with CG and NTAPG (p < 0.05). Inflammation, alveolar resorption, and cement damage were reduced significantly in the group treated with NTAP compared to the PG (p < 0.05). Significantly higher levels of osteoclasts were detected in the PG in comparison with both CG and NTAPG (p < 0.05). The lowest osteocalcin and ALP values were determined in PG, and the differences between PG and both groups were also significant (p < 0.05). CONCLUSION: Within the limitations of the present study, we can say that NTAP may enhance the bone remodeling process by inhibiting inflammation and preventing alveolar bone destruction. CLINICAL RELEVANCE: NTAP has clinical potential for accelerating and treating periodontitis with the inflammatory response modulation, osteoblast differentiation, and alveolar bone loss reduction.

Clinical, radiographic, and histological evaluation of three different pulp-capping materials in indirect pulp treatment of primary teeth: a randomized clinical trial.

OBJECTIVES: The aim of this randomized, controlled, three-arm parallel group, and double-blinded clinical trial was to evaluate the clinical, radiographic, and histopathological success of three different pulp-capping materials in one-stage indirect pulp treatment of primary teeth. MATERIALS AND METHODS: The study included a total of 109 patients aged 5-9 years who had primary teeth with deep carious lesions and symptoms of reversible pulpitis. The teeth were divided into three groups according to the pulp-capping agents: (I) hard-setting calcium hydroxide (Dycal) (control group) (n = 36), (II) bioactive tricalcium silicate (Biodentine) (n = 37), and (III) resin-based tricalcium silicate (TheraCal LC) (n = 36). All the teeth were evaluated clinically and radiographically at 6, 12, 18, and 24 months postoperatively. A total of 23 primary mandibular second molars that were in their regular exfoliation period (24-40 months) were extracted and fixed in 10% formaldehyde solution. The specimens were evaluated histologically to assess the integrity of the odontoblastic layer, tertiary dentin formation quality of the dentin formed, severity of pulpitis, and other pulpal changes. Data were analyzed using Fisher's exact test, Pearson's chi-square test, and McNemar's test (p = 0.05). RESULTS: At the end of the 24-month follow-up period, the clinical and radiographic success rates for Dycal, Biodentine, and TheraCal LC were 100%, 100%, and 93.3%, respectively, and there was no significant difference among the groups (p > 0.05). However, the TheraCal LC group was statistically unsuccessful when compared to the other groups with regard to the integrity of the odontoblastic layer, severity of pulpitis, and other pulpal changes in histological examination (p < 0.05). CONCLUSION: Indirect pulp capping exhibited high clinical and radiographic success rates in the treatment of primary teeth regardless of the chosen pulp-capping agent. However, histological examination indicated that the pulp status was affected by the chosen capping material especially when selecting a resin-containing material such as TheraCal LC. CLINICAL RELEVANCE: Resin-free calcium silicate-based materials appear to be more favorable in the indirect pulp treatment of primary teeth, particularly in young-age groups that require long-term success.

Effects of boric acid on bone formation after maxillary sinus floor augmentation in rabbits.

PURPOSE: Augmentation of the maxillary sinus floor with bone grafting is commonly used for successful treatment of edentulous posterior maxilla with dental implants, and it is essential to maintain good bone volume and quality for long-term success of dental implants. The aim of this experimental study was to investigate the local and systemic effects of boric acid on new bone formation after maxillary sinus floor augmentation (MSFA). MATERIALS AND METHODS: Twenty-four male, New Zealand rabbits were randomly divided into three groups with eight rabbits each, and bilateral MSFA was performed in each animal. An autogenous bone/xenograft mixture was used to augment the maxillary sinuses in each group. Group 1 was determined as control with no additional materials, whereas 3 mg/kg boric acid (BA) was added to the mixture in group 2, and 3 mg/kg boric acid solution added to drinking water daily in group 3. RESULTS: The animals were sacrificed and also histologic, histomorphometric, and immunnohistochemical analyses were performed at weeks 4 and 8. At week 4, bone regeneration was better in the local BA group than in the control and systemic BA groups (p < 0.05). However, no significant difference was found among the groups in terms of bone regeneration at the end of week 8 (p > 0.05). CONCLUSION: Significant higher new bone formation was revealed by BA at early healing especially with local application. BA may be a therapeutic option for improving the bone regeneration.

In Vitro Cytotoxicity of GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex.

INTRODUCTION: The aim of the present in vitro study was to evaluate the cytotoxicity of different sealers including GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex on L929 murine fibroblasts. METHODS AND MATERIALS: Samples of GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex were fabricated in Teflon disks of 5 mm diameter and 3 mm thickness. L929 fibroblasts were exposed to the extracts of these materials for 3, 24, 72 and 168 h at 37°C with 5% CO2. Cell viability was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The data were analysed by ANOVA. RESULTS: GuttaFlow Bioseal was nontoxic at all experimental time points (P>0.05), whereas MTA Fillapex and AH-Plus were toxic (P<0.001). At 7 days, there were more viable cells in the GuttaFlow 2 group than in the control group, and MTA Fillapex was more cytotoxic than AH-Plus. There were more apoptotic cells in the MTA Fillapex and AH-Plus groups than in the other groups at 3 h (P<0.001). CONCLUSION: GuttaFlow sealers are less cytotoxic than MTA Fillapex and AH-Plus. At all experimental time points, there was no significant difference in the cell viability between the GuttaFlow Bioseal group and the control group.