Evaluation of radiological and anatomical features of skull bones in adult Saanen goat.

BACKGROUND: Obtaining accurate knowledge of the anatomical structure of the skull helps in ontogenetic studies and determining sexual polymorphisms. OBJECTIVES: This study uses anatomical dissection and radiography to develop a size standard for the skull of the Saanen goat; information that will be applied to clinical evaluation and decision-making. METHODS: A total of 14 adult Saanen goat skulls (7 male and 7 female goats) were taken from the slaughterhouse and transferred to the clinic of the Faculty of Veterinary Medical Teaching Hospital, Urmia University, Urmia, Iran. Radiographs of each skull were prepared in the dorsal-ventral, left and right lateral recumbency. These heads were then brought over to the anatomy department, where the chosen morphometric traits were assessed and their means recorded. RESULTS: According to the findings of this study, the dorsal view of the skull revealed an incisive raphe and a widespread foramen of the nose. In the ventral view, the incisive bones were observed in the most cranial region of the skull. The base of the occipital bone was relatively large, and the jugular process was well-developed. In the lateral view, the incisive bone was extended to the cranial and had a narrow process on the dorsal surface. Regarding infra-orbital foramen, it was visible in the maxillary bone. Moreover, the lacrimal bone was perceived as a distinct bone. CONCLUSION: The precise standards acquired in this study can be utilized to interpret the findings and make clinical decisions about the normal and abnormal size of the bones that make up the skulls of the Saanen goats.

Optogenetics: A new tool for cancer investigation and treatment.

Despite the progress made in the diagnosis and treatment of cancer, it has remained the second cause of death in industrial countries. Cancer is a complex multifaceted disease with unique genomic and proteomic hallmarks. Optogenetics is a biological approach, in which the light-sensitive protein modules in combination with effector proteins that trigger reversibly fundamental cell functions without producing a long-term effect. The technology was first used to address some key issues in neurology. Later on, it was also used for other diseases such as cancer. In the case of cancer, there exist several signaling pathways with key proteins that are involved in the initiation and/or progression of cancer. Such aberrantly expressed proteins and the related signaling pathways need to be carefully investigated in terms of cancer diagnosis and treatment, which can be managed with optogenetic tools. Notably, optogenetics systems offer some advantages compared to the traditional methods, including spatial-temporal control of protein or gene expression, cost-effective and fewer off-target side effects, and reversibility potential. Such noticeable features make this technology a unique drug-free approach for diagnosis and treatment of cancer. It can be used to control tumor cells, which is a favorable technique to investigate the heterogeneous and complex features of cancerous cells. Remarkably, optogenetics approaches can provide us with outstanding tool to extend our understanding of how cells perceive, respond, and behave in meeting with complex signals, particularly in terms of cancer evasion from the anticancer immune system functions.

Overexpression of GDNF and FGF-1 in Canine Benign Prostatic Hyperplasia: Evidence for a Pathogenetic Role of Neural Growth Factor.

Benign prostatic hyperplasia (BPH) is common in aged dogs, but the pathogenesis has not been clearly elucidated. A total of 33 male Iranian dogs of mixed breed and in three age groups (under 3 years [n = 10]; 3-6 years [n = 15]; over 6 years [n = 8]), were investigated. BPH was confirmed by ultrasonography and histopathology in 13 cases. The highest prevalence of BPH was in the 3-6 years age group (8/15; 53.3%). Examination of sections of prostate that had been stained with Masson's trichrome revealed that the intensity of stromal smooth muscle cell staining (P <0.05) and the number of fibroblasts (P = 0.002) were significantly increased in BPH compared with normal prostate glands. Prostate cells from dogs with BPH (n = 13) had a significantly higher intensity of cytoplasmic immunolabelling with antibodies against glial cell line-derived neurotrophic factor (GDNF), cytokeratin (CK) AE1/AE3, vimentin, fibroblast growth factor-1 (FGF-1) and prostate-specific antigen (PSA), compared with normal prostate glands (n = 20) (P = 0.001), except for PSA, which was negative in both normal and BPH affected prostates. The overexpression of GDNF and FGF-1 in stromal and epithelial cells of prostate glands of dogs with BPH suggests that GDNF has a paracrine or autocrine role in stimulating cellular proliferation. GDNF overexpression may also play a pathogenetic role in promoting chronic prostatitis and increasing fibrosis and the smooth muscle component of the prostate gland in BPH.

Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways.

OBJECTIVES: Chemotherapies used to treat colon cancer might often fail due to the emergence of chemoresistance and side effects. Escherichia coli Nissle 1917 (EcN) is a beneficial probiotic, whose molecular mechanisms in the prevention of colon cancer are yet to be fully understood. The present study assessed the anti-cancer effects of EcN treatments in human colorectal cancer, HT-29 cell line, with the analysis of related mechanisms. MATERIALS AND METHODS: The co-culture conditioned-media (CM) of EcN with adenocarcinoma HT-29 cells and heat-inactivated bacteria (HIB) were applied for the treatment of the HT-29 cells. To study the inhibition potential of CM and HIB on cancer cells, various cellular/molecular analyses were implemented, including DAPI-staining and DNA ladder assays, flow cytometry and Real-time quantitative PCR (qPCR), as well as Western blotting analyses. RESULTS: Our results indicated that EcN could elicit apoptotic impacts on the colon cancer HT-29 cells by up-regulating PTEN and Bax and down-regulating AKT1 and Bcl-xL genes. CONCLUSION: Based on our findings, EcN is proposed as a useful supplemental probiotic treatment against colon cancer.

Designing a light-activated recombinant alpha hemolysin for colorectal cancer targeting.

Introduction: Colorectal cancer (CRC) is one of the main health burden worldwide, which can cause major economic and physiological problems along with relatively high rate of mortality. It is important to develop new methods for the localized delivery of recombinant protein therapeutics, in large part due to the failure of conventional therapies in most cases. Since E. coli Nissle 1917 (EcN) does not produce any virulence factors, here we used these bacteria with the light-activated promoter system to deliver therapeutic agents in the desired location and time. Methods: In this study, Staphylococcus aureus alpha hemolysin (SAH), after codon usage optimization, was cloned into blue light activating vector (pDawn) and transferred to EcN strain. Then, the functionality and cytotoxicity of secreted alpha hemolysin was evaluated in the SW480 colon cancer cell line by using different experiments, including blood agar test, flow cytometry analysis, and DAPI staining. Results: Our findings revealed that EcN can produce functional SAH under the blue light irradiation against SW480 cancer cells. Moreover, cytotoxicity assays confirmed the dose- and time-dependent toxicity of this payload (SAH) against SW480 cancer cells. Conclusion: Based on our results, EcN is proposed as an appropriate light-activated vehicle for delivery of anticancer agents to the target cancer cells/tissues.

Bioengineered smart bacterial carriers for combinational targeted therapy of solid tumours.

Despite many endeavours for the development of new anticancer drugs, effective therapy of solid tumours remains a challenging issue. The current cancer chemotherapies may associate with two important limitations, including the lack/trivial specificity of treatment modalities towards diseased cells/tissues resulting in undesired side effects, and the emergence of drug-resistance mechanisms by tumour cells causing the failure of the treatment. Much attention, therefore, has currently been paid to develop smart and highly specific anticancer agents with maximal therapeutic impacts and minimal side effects. Among various strategies used to target cancer cells, bacteria-based cancer therapies (BCTs) have been validated as potential gene/drug delivery carriers, which can also be engineered to be used in diagnosis processes. They can be devised to selectively target the tumour microenvironment (TME), within which they may preferentially proliferate in the necrotic and anaerobic parts - often inaccessible to other therapeutics. BCTs are capable to sense and respond to the environmental signals, upon which they are considered as smart microrobots applicable in the controlled delivery of therapeutic agents to the TME. In this review, we aimed to provide comprehensive insights into the potentials of the bioengineered bacteria as smart and targeted bio-carriers and discuss their applications in cancer therapy.

Reliability modelling of redundant safety systems without automatic diagnostics incorporating common cause failures and process demand.

Redundant safety systems are commonly used in the process industry to respond to hazardous events. In redundant systems composed of identical units, Common Cause Failures (CCFs) can significantly influence system performance with regards to reliability and safety. However, their impact has been overlooked due to the inherent complexity of modelling common cause induced failures. This article develops a reliability model for a redundant safety system using Markov analysis approach. The proposed model incorporates process demands in conjunction with CCF for the first time and evaluates their impacts on the reliability quantification of safety systems without automatic diagnostics. The reliability of the Markov model is quantified by considering the Probability of Failure on Demand (PFD) as a measure for low demand systems. The safety performance of the model is analysed using Hazardous Event Frequency (HEF) to evaluate the frequency of entering a hazardous state that will lead to an accident if the situation is not controlled. The utilisation of Markov model for a simple case study of a pressure protection system is demonstrated and it is shown that the proposed approach gives a sufficiently accurate result for all demand rates, durations, component failure rates and corresponding repair rates for low demand mode of operation. The Markov model proposed in this paper assumes the absence of automatic diagnostics, along with multiple stage repair strategy for CCFs and restoration of the system from hazardous state to the "as good as new" state.

Potential of microalgae and lactobacilli in biosynthesis of silver nanoparticles.

INTRODUCTION: Application of nanoparticles has been extensively increased in last decades. Nanoparticles of noble metals such as gold, platinum and especially silver are widely applied in medical and pharmaceutical applications. Although, variety of physical and chemical methods has been developed for production of metal nanoparticles, because of destructive effects of them on environment, biosynthetic methods have been suggested as a novel alternative. Some bacteria and microalgae have different ranges of potentiality to uptake metal ions and produce nanoparticles during detoxification process. In the present work, we study the potential of three Lactobacilli and three algal species in production of AgNPs in different concentrations of silver nitrate. METHODS: Utilizing AAS, XRD and TEM methods, Nannochloropsis oculata, Dunaliella salina and Chlorella vulgaris as three algal species in addition to three Lactobacilli including L. acidophilus, L. casei, L. reuteri were monitored for production of silver nanoparticles. Three concentrations of AgNO3 (0.001, 0.002, 0.005 M) and two incubation times (24h and 48h) were included in this study. RESULTS: Our findings demonstrated that C. vulgaris, N. oculata and L. acidophilus have the potential of nanosilver production in a culture medium containing 0.001 M of AgNO3 within 24 hours. Also L. casei and L. reuteri species exhibited their potential for production of silver nanoparticles in 0.002 M concentration of AgNO3 in 24 hours. The size range of particles was approximately less than 15 nm. The uptake rate of silver in the five species was between 1.0 to 2.7 mg/g of dry weight. Nanoparticle production was not detected in other treatments and the algae Dunaliella. CONCLUSION: The biosynthesis of silver nanoparticles in all of three Lactobacilli and two algal species including N. oculata and C. vulgaris was confirmed.