CRISPR/Cas9-mediated knockout of MLL5 enhances apoptotic effect of cisplatin in HeLa cells in vitro

Mixed lineage leukemia 5 (MLL5) transactivates the expression of E6 and E7 oncogenes in cervical cancer cells. In this study, we utilized ‎CRISPR/Cas9 system with the aim to target HPV-E6 and MLL5 to enhance apoptosis efficiency in HPV-18 positive HeLa cells and to improve chemotherapeutic efficacy of Cisplatin as the most common anticancer drug, used for cervical cancer. ‎sgRNAs against MLL5 and E6 were designed and cloned into PX458 plasmid vector. ‎Real-time ‎PCR was used to determine knockout expression of MLL5 and E6 following, ‎transfection with cloned plasmids. Cell viability and apoptosis were evaluated, using ‎Dimethyl-thiazolyl diphenyl tetrazolium bromide (MTT) ‎assay and Annexin V flow cytometry. ‎‏Cellular p‎53 level was measured, using enzyme linked immune sorbent assay (ELISA).‏ Real-time ‎PCR indicated the downregulation of E6 and MLL5 in the transfected cells. ‎A significant increase in the accumulation of P53 was observed due to targeting MLL5 and E6 genes. MTT and ‎apoptosis assays showed a significant decrease in cell viability and enhanced apoptosis rate of ‎transfected cells. Combination therapy showed that targeting E6 and MLL5 enhanced ‎apoptotic effect of Cisplatin in MLL5 knockout cells in a synergistic manner. ‎‏The results suggest that CRISPR/Cas9 targeting of E6 and MLL5 genes can increase‎ apoptotic effects of Cisplatin and can be considered as a ‎‎potential combination therapy for the treatment of HPV-‎related cervical cancer.

Hierarchical Decision-making using a New Mathematical Model based on the Best-worst Method

Decision-making processes in different organizations often have a hierarchical and multilevel structure with various criteria and sub-criteria. The application of hierarchical decision-making has been increased in recent years in many different areas. Researchers have used different hierarchical decision-making methods through mathematical modeling. The best-worst method (BWM) is a multi-criteria evaluation methodology based on pairwise comparisons. In this paper, we introduce a new hierarchical BWM (HBWM) which consists of seven steps. In this new approach, the weights of the criteria and sub-criteria are obtained by using a novel integrated mathematical model. To analyze the proposed model, two numerical examples are provided. To show the performance of the introduced approach, a comparison is also made between the results of the HBWM and BWM methodologies. The analysis demonstrates that HBWM can effectively determine the weights of criteria and sub-criteria through an integrated model

Toward Real-Time Image Annotation Using Marginalized Coupled Dictionary Learning

In most image retrieval systems, images include various high-level semantics, called tags or annotations. Virtually all the state-of-the-art image annotation methods that handle imbalanced labeling are search-based techniques which are time-consuming. In this paper, a novel coupled dictionary learning approach is proposed to learn a limited number of visual prototypes and their corresponding semantics simultaneously. This approach leads to a real-time image annotation procedure. Another contribution of this paper is that utilizes a marginalized loss function instead of the squared loss function that is inappropriate for image annotation with imbalanced labels. We have employed a marginalized loss function in our method to leverage a simple and effective method of prototype updating. Meanwhile, we have introduced ${\ell}_1$ regularization on semantic prototypes to preserve the sparse and imbalanced nature of labels in learned semantic prototypes. Finally, comprehensive experimental results on various datasets demonstrate the efficiency of the proposed method for image annotation tasks in terms of accuracy and time. The reference implementation is publicly available on https://github.com/hamid-amiri/MCDL-Image-Annotation.Comment: @article{roostaiyan2022toward, title={Toward real-time image annotation using marginalized coupled dictionary learning}, author={Roostaiyan, Seyed Mahdi and Hosseini, Mohammad Mehdi and Kashani, Mahya Mohammadi and Amiri, S Hamid}, journal={Journal of Real-Time Image Processing}, volume={19}, number={3}, pages={623--638}, year={2022}, publisher={Springer}

Psychometric evaluation of the health-seeking behavior scale based on Kroeger’s model for elective cardiac interventions

Background: Coronary artery bypass graft surgery (CABG) is one of the two most commonly used interventions for Myocardial Reperfusion. Studies suggest that the existence and direction of the effect of the factors affecting health-seeking behavior depend on the context of each society. Thus, this study aimed to introduce and validate a tool for investigating the factors affecting the health-seeking behavior of patients requiring a cardiovascular intervention as a prerequisite for planning and policymaking.   Methods: By reviewing the literature and questionnaires previously used in the field of health-seeking behavior and the patient's decision-making process, a set of related questions was collected based on Kroeger’s model variables. Ten content experts were requested to evaluate each item and then content validity ratio (CVR) and content validity index (CVI) were calculated and used for instrument modification. Participants were included through a convenience sampling procedure. Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) was used to assess construct validity. Cronbach's alpha coefficient was used to measure instrument reliability.   Results: Of the 142 participants, 79 (55.5%) were male. Through the validation process, a hierarchical model with four factors and 20 items with three error covariance (accounting for 63.06 present of outcome variable variation) was confirmed. Also, an examination of the four constructs obtained with Cronbach's alpha coefficient was more than 0.8 indicating acceptable reliability.   Conclusion: Findings suggest that the designed scale of health-seeking behavior based on Kroeger’s model is a reliable and valid scale among the Iranian population

Comparison of Visual Evoked Potential and Electro-oculogram Tests in Early Detection of Hydroxychloroquine Retinal Toxicity

Purpose: To compare the sensitivity of visual evoked potential (VEP) and electro-oculogram (EOG) tests in early detection of hydroxychloroquine (HCQ) retinal toxicity.Patients and Methods: In this prospective cross-sectional study, 100 consecutive patients (age range: 18 to 30) with juvenile rheumatoid arteritis (JRA) and a cumulative hydroxychloroquine dosage of at least 200gr were included.  In addition 100 healthy individuals with matched age and sex were included as controls. Ocular examinations including visual acuity testing, refractive errors measurement, applanation tonometry, slit lamp biomicroscopy fundus ophthalmoscopy and electrophysiological examinations (EOG and VEP) were performed in both groups. Scores of less than 1.8 for the Arden Index in EOG (AI), as well as less than 4mv of P100 amplitude and more than 110ms of P100 latency in VEP were considered abnormal.Results: The mean cumulative dosage of HCQ among participants was 262.4±31.9g (95% CI: 256.1 to 268.8g). The mean measurement of AI (EOG), P100 latency and amplitude of VEP were 1.8±0.4, 112.7±10.1ms and 3.7±2.1mv, respectively. There was a significant difference between case and control groups in all parameters (p<0.001 for all). There was not any significant difference between AI (EOG), P100 latency and amplitude of VEP in detecting the ocular toxicity due to HCQ.Conclusion: We conclude that AI (EOG), P100 amplitude and latency of VEP can all be useful parameters to detect HCQ retinal toxicity, and we did not detect any difference between these two methods.

A sub-threshold differential cmos schmitt trigger with adjustable hysteresis based on body bias technique

This paper presents a sub-threshold differential CMOS Schmitt trigger with tunable hysteresis, which can be used to enhance the noise immunity of low-power electronic systems. By exploiting the body bias technique to the positive feedback transistors, the hysteresis of the proposed Schmitt trigger is generated, and it can be adjusted by the applied bias voltage to the bulk terminal of the utilized PMOS transistors. The principle of operation and the main formulas of the proposed circuit are discussed. The circuit is designed in a 0.18-μm standard CMOS process with a 0.6 V power supply. Post-layout simulation results show that the hysteresis width of the Schmitt trigger can be adjusted from 45.5 mV to 162 mV where the ratio of the hysteresis width variation to supply voltage is 19.4%. This circuit consumes 10.52 × 7.91 μm2 of silicon area, and its power consumption is only 1.38 μW, which makes it a suitable candidate for low-power applications such as portable electronic, biomedical, and bio-implantable systems

Investigating the relationship between carotid intima-media thickness, flow-mediated dilatation in brachial artery and nuclear heart scan in patients with rheumatoid arthritis for evaluation of asymptomatic cardiac ischemia and atherosclerotic changes

Background: Cardiovascular disease is the most common cause of death worldwide. In order to prevent and treat heart diseases, we need to estimate the trend of non-cardiac diseases with the cardiovascular system. Arthritis Rheumatoid is a chronic immune/inflammatory process which leads to subclinical atherosclerosis and increases cardiovascular disease. We examined the patients who referred to our nuclear medicine center for MPI and correlated their findings with flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thickness (CIMT) in arthritis rheumatoid patients. Material and methods: A total 30 known cases with arthritis rheumatoid were referred to our department for MPI and the single-photon emission computed tomography (SPECT) imaging were visually and quantitatively evaluated by two nuclear medicine physicians and the correlation of the measured FMD and CIMT were evaluated and compared with ultrasonography data. Demographic information such as gender, age and sex and medical history (risk factors, cardiovascular sign and symptoms, lab findings, medication etc…) were recorded in questionnaire sheets and were analyzed by SPSS.20. Chi-square and student t-test were used for further analysis. Results: The mean CIMT (R = 0.452 ± 0.07, L = 0.447 ± 0.08) and %FMD (R = 7.22 ± 8.66, L = 6.42 ± 11.88) were measured for all subjects. Age was the only parameter correlated with both right and left CIMT (P = 0.033 and P = 0.024, respectively). Among the patients, 26.7% had mild ischemia (SSS < 8) and 3 of them suffered from active arthritis rheumatoid. All patients with RA showed normal ventricular ejection fraction and normal volumes and among them, 93.3% had normal functional performance (normal wall motion…). Moreover, the mean CIMT and %FMD were not significantly different in ischemic and non-ischemic patients. Among ischemic patients, just the course of the disease was associated with CIMT and none of the parameters was correlated with FMD. Conclusions: There is no significant statistical difference between ischemic and non-ischemic patients and also the functional performance with values of CIMT and FMD. Among all populations, the parameter of age, and in ischemic group, the course of disease were found as the only variable correlated with CIMT

Antitumor effects of a recombinant baculovirus displaying anti-HER2 scFv expressing Apoptin in HER2 positive SK-BR-3 breast cancer cells

Aim: Since HER2 targeted therapies have shown clinical benefit in breast cancer, in the present study recombinant baculovirus (BV) displaying anti-HER2 single-chain variable domain fragment (scFv) expressing Apoptin was generated. Methods: The binding specificity and surface display of anti-HER2 scFv were evaluated using enzyme-linked immunosorbent andassay (ELISA) and electron microscopy, respectively. The targeting properties and cytotoxic effect on breast cancer cells determined by fluorescence microscopy and MTT assays. Results: The results demonstrated that recombinant BV could specifically bind to HER2-overexpressing SK-BR-3 cells but not to the HER2 negative MCF-7 cells and reduced the viability of SK-BR-3 cells by expressing Apoptin. Conclusion: These results suggest that the antitumor effect of Apoptin in combination with HER2 targeting of this recombinant BV makes it a promising vector in targeted cancer therap

Role of Selective Cyclooxygenase-2 Inhibitors in Renal Colic Pain Reduction and Improvement: A Systematic Review of Clinical Trials

Renal colic is an irritating condition that develops after obstruction of the ureter. Selective cyclooxygenase-2 inhibitors are types of non-steroidal anti-inflammatory drugs (NSAIDs) that have beneficial role in treatment various diseases. Hence, this systematic review summarizes the current knowledge about the role of selective cyclooxygenase-2 (COX-2) inhibitors as painkiller in renal colic pain management. The present systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements. Until September 2022, PubMed/Medline, Scopus, Web of Science, and Google Scholar databases were searched using the relevant keywords including “Selective Cyclooxygenase-2 Inhibitors”, “Parecoxib”, “Celecoxib”, “Rofecoxib”, “Renal Colic Pain” and “Ureteral Colic Pain”. Of 64 identified records through database searching, 6 randomized controlled trials (RCTs) were selected for this systematic review. The sample size in RCTs were between 53 and 338. The range of subject’s age was from 18 to 69. Overall, the evidence of this review revealed that the selective COX-2 inhibitors particularly celecoxib and parecoxib could alleviate renal colic pain in most of the studies through decreasing relevant pain score. Overall, selective COX-2 inhibitors seem to be effective in alleviating renal colic pain. However, further high quality assessments are required for demonstrating therapeutic role of selective COX-2 inhibitors against renal colic pain.             Keywords: Anti-Inflammatory Agents; Non-Steroidal; Renal Colic; Pain Management