The Effect of Slime Factor in the Treatment of Spinal Implant Infections.

AIM: To investigate the effect of the biofilm-forming ability of the bacteria on treatment in rats by using biofilm-forming and nonbiofilm- forming strains of Staphylococcus aureus (S. aureus). MATERIAL AND METHODS: Forty rats were divided into four equal groups as Group 1A, 1B, 2A, and 2B. All rats underwent single distance lumbar laminectomy, and titanium implants were introduced. Group 1 rats were inoculated with Slime factor (-) S. aureus, while Group 2 rats were inoculated with biofilm Slime factor (+) S. aureus. None of the rats were given antibiotics. One week later, the surgical field was reopened and microbiological samples were taken. The implants of rats in Groups 1A and 2A were left in place, while the implants of rats in Groups 1B and 2B were removed. RESULTS: There was no statistically significant difference between the groups inoculated with slime factor (+) S. aureus; although, Groups 1A and 2A showed statistically significant difference. Statistical analysis with respect to bacterial count also showed a statistically significant difference between Groups 1A and 2A. There was a statistically significant difference between Group 1B and 2B. CONCLUSION: The results obtained in the present study reveal that in case of implant-dependent infection, the first sample taken can be checked for slime factor, and if there is infection with slime factor-negative bacterium, treatment without removing the implant may be recommended. S. aureus was used in the study because it is the most common cause of implant-related infection at surgical sites. Further studies using different bacterial species are needed to reach a definitive conclusion.

Promoter Hypomethylation Upregulates ANXA2 Expression in Pancreatic Cancer and is Associated with Poor Prognosis.

Pancreatic cancer (PC) is one of the world's most aggressive and deadly cancers, owing to non-specific early clinical symptoms, late-stage diagnosis, and poor survival. Therefore, it is critical to identify specific biomarkers for its early diagnosis. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein that has been reported to be upregulated in several cancer types, making it an emerging biomarker and potential cancer therapeutic target. However, the mechanism underlying the regulation of ANXA2 overexpression is still unclear. It is well established that genetic and epigenetic alterations may lead to widespread dysregulation of gene expression. Hence, in this study, we focused on exploring the regulatory mechanism of ANXA2 by investigating the transcriptional profile, methylation pattern, somatic mutation, and prognostic value of ANXA2 in PC using several bioinformatics databases. Our results revealed that the expression levels of ANXA2 were remarkably increased in PC tissues comparing to normal tissues. Furthermore, the high expression of ANXA2 was significantly related to the poor prognosis of PC patients. More importantly, we demonstrated for the first time that the ANXA2 promoter is hypomethylated in PC tissues compared to normal tissues which may result in ANXA2 overexpression in PC. However, more experimental research is required to corroborate our findings.

Combination treatment of bortezomib and epirubicin increases the expression of TNFRSF10 A/B, and induces TRAIL-mediated cell death in colorectal cancer cells.

Colorectal cancer is one of the most common cancers worldwide, affecting the colon and rectum. A major problem in the treatment of colorectal cancer is acquired chemoresistance, including resistance against death receptor-induced apoptosis. Therefore, investigating new biomarkers for the treatment of the disease and sensitization strategies against TRAIL might be of high clinical importance. TNFRSF10A/B are known as death receptors for TRAIL-induced apoptotic cell death. In this study, we used multiple bioinformatic tools and experimental analyses to investigate the role of TRAIL receptors TNFRSF10A and TNFRSF10B in colorectal cancer. We also identified the potential effect of bortezomib and epirubicin in the induction of TRAIL-mediated apoptotic cell death. Here, we showed that TNFRSF10 A/B expressions are upregulated in various tumor types, including COAD, and its high expression is decreased with the different clinicopathological parameters in COAD. We also found an association between TNFRSF10 A/B expression and tumor molecular subtypes. We further detected the association between the expression of TNFRSF10 A/B and immune cell tumor infiltration, including B cells, CD8+ T cells, neutrophils and dendritic cells. In addition, we showed that combining bortezomib and epirubicin treatment leads to the upregulation of TNFRSF10 A/B in colorectal cancer cells in vitro. The increase in the expression of death receptors was correlated with higher active caspase-3 levels following the incubation of cells with recombinant TRAIL protein, which is a ligand for TNFRSF10 A/B receptors. Our results suggest that TNFRSF10 A/B may be a marker to differentiate tumor molecular subtypes in colorectal cancer. The expression of TNFRSF10 A/B may be associated with the recruitment of immune cells into tumors and the development of tumor suppression. The combination of bortezomib and epirubicin treatment might sensitize colorectal cancer cells to TRAIL-induced apoptosis via the upregulation of death receptor.

Eco-friendly Synthesis and Characterization of Silver Nanoparticles using Juglans regia Extract and their Anti-Trichomonas vaginalis, Anticancer, and Antimicrobial Effects.

BACKGROUND: Green synthesis is an efficient and eco-friendly method that has been used frequently in silver nanoparticle production in recent years. This method facilitates the production of nanoparticles using various organisms, such as plants, and is also cheaper and easier to apply than the other techniques. AIMS: This study aims to find possible mechanisms and pharmacological effects of cubic silver nanoparticles (AgNPs). OBJECTIVES: This study characterizes cubic AgNPs and describes in detail their anticancer, antimicrobial, and anti- Trichomonas vaginalis abilities. METHODS: Silver nanoparticles were produced by green synthesis using Juglans regia (walnut) leaf aqueous extract. We validated the formation of AgNPs by UV-vis spectroscopy, FTIR analysis, and SEM micrographs. To determine the pharmacological effects of the AgNPs, we conducted anti-cancer, anti-bacterial, and anti-parasitic activity experiments. RESULTS: Cytotoxicity data revealed that AgNPs have cellular inhibitory properties on cancerous MCF7 (breast), HeLa (cervix), C6 (glioma), and HT29 (colorectal) cell lines. Similar results are also obtained with anti-bacterial and anti- Trichomonas vaginalis activity experiments. At certain concentrations, AgNPs displayed stronger anti-bacterial activities than the sulbactam/cefoperazone antibiotic combination in five bacteria species. Furthermore, the 12-h AgNPs treatment exhibited satisfactory anti-Trichomonas vaginalis activity similar to the FDA-approved metronidazole. CONCLUSION: Consequently, AgNPs produced by the green synthesis method by Juglans regia leaves showed remarkable anti-carcinogenic, anti-bacterial, and anti-trichomonas vaginalis activities. We propose the potential usefulness of green synthesized AgNPs as therapeutics.

Expressional regulation of NKG2DLs is associated with the tumor development and shortened overall survival in lung adenocarcinoma.

Natural killer group 2D ligands (NKG2DLs) are expressed on tumor cells as a ligand for Natural killer group 2D (NKG2D) receptors. NKG2DLs interact with NKG2D to induce immune cell-mediated cytotoxicity for eliminating tumors. Studies demonstrated that tumor cells can reduce NKG2DLs' expression to escape from anti-tumor immunity, leading to an aggressive cancer phenotype and poor prognosis in some cancers. However, these studies are limited and there is no comprehensive work on the regulation of NKG2DLs in lung adenocarcinoma (LUAD) which is one of the deadliest cancers worldwide. Here, we conducted an in silico analysis to evaluate the changes in NKG2DLs in LUAD by analyzing The Cancer Genome Atlas and the Gene Expression Omnibus datasets including tumor vs. normal comparisons, TNM stages, survival and infiltrating immune estimation profile. Results indicated that some members of NKG2DL were downregulated in LUAD as compared to normal samples. We determined that MICA (MHC class I polypeptide-related sequence A) was the most and significantly downregulated ligand among others and the results were nearly consistent with the different datasets which we used. Furthermore, survival analysis revealed that down-regulated MICA transcript expression might be one of the prognostic indicators of LUAD. Interestingly, according to the immune cell infiltrating analysis, there wasn't a direct correlation between the MICA transcript expression and immune cell infiltration, while for MICB there was. In addition, in genetic alteration, DNA methylation and miRNA analyses, we did not observe critical outcomes that would clarify the down-regulated MICA expression in detail. Regardless, this study is highly comprehensive and contributes valuable suggestions to further functional studies about the regulation of NKG2DLs and promising immunotherapeutic approaches in LUAD.

Expression profiles of Natural Killer Group 2D Ligands (NGK2DLs) in colorectal carcinoma and changes in response to chemotherapeutic agents.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Natural Killer Group 2D Receptor (NKG2D) and their ligands (NKG2DLs) play crucial roles in natural killer (NK) cell-mediated cytotoxicity. Tumorigeneses cause increased NKG2DLs expression on tumor cell surfaces, thereby these cells individually eliminated by NK cells. However, CRC cells can reduce their NKG2DL expression to escape from NK-mediated immune surveillance which is associated with poor prognosis. Therefore, previous studies suggest that up-regulation of NKG2DLs can contribute to promising NK cell-mediated immunotherapy strategies. We aimed to analyze NKG2DLs expression profiles in response to chemotherapeutic drugs and increased MHC class I polypeptide-related sequence A (MICA) expression, which is related to favorable prognosis in CRC, using low doses of bortezomib and epirubicin combination without causing direct cytotoxicity. Results showed that MICA expression  sligthly increased following drug treatment in the CRC cells but not for the normal cells. Also, we enriched our study with Gene Expression Omnibus (GEO) datasets including expression profiles of various NKG2DLs using in silico analyses. Accordingly, NKG2DL expression in CRC was screened in proportion to other cancers, histologic subtypes, TNM stages and metastatic samples to compare with our data. Overall, the analyzed data showed that NKG2DLs demonstrate different expression profiles in response to chemotherapeutic agents and a combination of low-dose bortezomib and epirubicin slightly increased MICA mRNA expression in CRC cell lines. However, performing further analysis of the combination therapy for MICA protein expression and studying its interaction with NK cells will make the results more meaningful.

A broad analysis in clinical and in vitro models on regulator of G-protein signalling 10 regulation that is associated with ovarian cancer progression and chemoresistance.

Ovarian cancer is one of the deadliest types of gynaecological cancers and more than half of the patients die within 5 years after diagnosis. Recurrence in advanced staged patients after chemotherapy is associated with increased chemoresistance, which results in poor prognosis. Regulator of G-protein signalling 10 (RGS10) negatively regulates cell proliferation, migration and survival by attenuating G-protein coupled-receptors mediated signalling pathways. Recent studies have shown that loss of RGS10 expression is significantly associated with proliferation and cisplatin resistance in ovarian cancer cells. SIGNIFICANCE OF THE STUDY: In this study, we analysed differential RGS10 expression levels using public microarray datasets from clinical and in vitro ovarian cancer samples. We validated that cancer progression and chemotherapy exposure change RGS10 expression. We enriched our study to evaluate the relationship between chemoresistance and differential RGS10 expression against ovarian cancer potential chemotherapeutic agent, palbociclib. Results showed that palbociclib treatment reduced cell viability, despite significantly decreased RGS10 expression in chemoresistant cells. Overall, the results confirmed that cancer progression and chemoresistance are significantly associated with the down-regulation of RGS10 while some chemotherapeutics seem to be beneficial in decreasing chemoresistance in ovarian cancer.