The Anticancer Potential of Ivermectin: Mechanisms of Action and Therapeutic Implications

Abstract Ivermectin is a well-known antiparasitic drug in the macrolide class with a 16-membered ring. It has been used for treating various parasitic diseases, including onchocerciasis, lymphatic filariasis, and strongyloidiasis. The present study aimed to review the mechanisms of action and therapeutic implications of Ivermectin as an anticancer agent. It has been used for over three decades, and its safety has been well-established in humans A growing body of evidence suggests that ivermectin has anticancer properties, making it an attractive candidate for treating various types of cancer. The reason is that ivermectin targets multiple signaling pathways, including the Wnt/β-catenin, PI3K/Akt/mTOR, and STAT3 pathways, to inhibit cancer cell proliferation and induce apoptosis. Inhibition of these pathways by ivermectin leads to suppression of cancer cell growth. Additionally, ivermectin has been shown to induce autophagy, which can lead to programmed cell death in cancer cells. One of the significant advantages of ivermectin as an anticancer drug is its safety profile. Furthermore, it is easily available and affordable, making it a promising alternative to conventional chemotherapy for various types of cancer, including breast, lung, and colon cancer. However, further research is needed to evaluate its clinical effectiveness in humans. Clinical trials are underway to investigate ivermectin's safety and efficacy in cancer treatment. In conclusion, the safety profile and low cost of ivermectin as an anticancer drug have turned it into a feasible alternative to conventional chemotherapy, which needs more investigation. https://jlar.rovedar.com/index.php/JLAR/article/view/1

Motivation-based Market Segmentation in Rural Tourism: the Case of Sámán, Iran

Market segmentation is a pivotal and under-investigated issue when evaluating decision-making processes and motivational factors shaping rural tourism. The present study has examined market segments of rural tourists in Iran based on their socio-demographic attributes, travel characteristics and preferred leisure activities, profiling rural tourists on the base of their motivational background. The survey results indicated that rural tourism in the study area is a heterogeneous market, whose development depends on general trends in Middle East tourism market. A comprehensive knowledge of rural tourism actors may help formulating appropriate marketing strategies for internal areas destined to tourism growth

CRISPR/Cas9-mediated Genome Editing: In vivo Review

Abstract The CRISPR/Cas9 system has been a game-changer in genetics and biotechnology. This study aimed to investigate the existing in vivo uses and their potential to increase our understanding of gene function and biological processes in animal models. With its remarkable precision and accuracy, researchers can now easily edit specific genes within cells and organisms. This technology has opened up new avenues for studying genetic diseases and developing therapies to treat them. One of the most significant advantages of the CRISPR/Cas9 system is its ability to create precise cellular and animal models of human diseases. This allows researchers to investigate the role of genetics in disease development and to develop more effective therapies. For example, the system can correct genetic mutations that cause cystic fibrosis or sickle cell anemia. The therapeutic potential of CRISPR/Cas9 is enormous, especially in gene therapy. By correcting specific genetic mutations, the system can potentially treat human diseases that are currently untreatable with conventional therapies. However, some challenges still need to be addressed before this technology can be used in clinical settings. Despite these challenges, the potential of CRISPR/Cas9 to revolutionize the field of genetics and biotechnology cannot be overstated. Ultimately, this technology has the potential to transform medicine by providing new therapies for a wide range of genetic diseases. https://jlar.rovedar.com/index.php/JLAR/article/view/1

Toxicity and biological impact of metal and metal oxide nanoparticles : Focus on the vascular toxicity of ultra-small titanium dioxide nanoparticles

The application of nanoparticles (NPs) in different technologies has led to tremendous advancement in those fields.  Moreover, there is growing interest in application of ultra-small NPs (USNPs) at 1-3 nm due to their distinct molecule like features. Parallel to these promises, there is a growing concern regarding their safety. The main goal of this thesis was to investigate the toxicity and underlying mechanisms following exposure to different metal and metal oxide NPs as well as USNPs. Their effects were studied on Saccharomyces cerevisiae, on hepatocytes and endothelial cells and finally in vivo on zebrafish embryos (Danio rerio). By selecting the rutile form of titanium dioxide (TiO2-USNPs) without intrinsic or intracellular reactive oxygen species (ROS) production, we could study biological impacts solely due to size and direct interaction with the cells. We showed that TiO2-USNPs were not cytotoxic but induced DNA damage. They had anti-angiogenic effects both in vitro and in vivo. Also, at high concentrations they caused complete mortality in zebrafish embryos exposed in water, while at lower concentrations induced delay in hatching. When injected they caused malformations. They specifically induced the differential overexpression of transcripts involved in lipid and cholesterol metabolism in endothelial cells. In hepatocytes they induced the overexpression of proteins in the electron transport chain and decreased lipids in lipid rafts. At 30 nm, TiO2-NPs, were also not cytotoxic but were genotoxic. They had no effects in vivo or on angiogenesis. However, they induced differential expression of transcripts involved in endoplasmic reticulum (ER) stress and heat shock response as well as cholesterol metabolism. This suggests a more toxic response in the cells compared to TiO2-USNPs.  Single walled carbon nanotubes (SWCNTs) despite having the highest oxidative activity among the NPs studied, were not severely cyto- or genotoxic but induced expression of transcripts involved in early ER stress response. Copper oxide (CuO-NPs) was the most toxic NPs studied due to both ion release and ROS production, affecting lipid metabolism of the cells. Silver (Ag-NPs) were also cytotoxic and caused the disruption of cellular components and lipids. ZnO-NPs were not cytotoxic, did not affect cellular lipids but they increased the size of vacuoles in yeast cells. Finally by using superparamagnetic iron oxide NPs (SPIONs) with different coatings, and using a mathematical model, a nano impact index (INI) was developed as a tool to enable the comparison of nanotoxicology data.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 3: Manuscript. Paper 4: Manuscript. Paper 5: Manuscript.</p

The Early Prelinguistic Skills in Iranian Infants and Toddlers

Objectives: The prelinguistic skills which pave the way for language development have always been an area of research in the Speech Therapy field. Although studying these skills is important, there is a study gap among Persian children. Therefore, this study explored prelinguistic skills among a sample of Persian-speaking children aged 6 to 24 months and made a comparison between different age groups. We also studied the effects of gender and family history of speech-language disorders on children’s prelinguistic abilities.  Methods: In the present study, 277 mothers of Iranian Persian-speaking children aged 6 to 24 months were asked to fill a research-made checklist that evaluated the prelinguistic skills of their children. This study was cross-sectional and was conducted in Tehran City, Iran, in 2021. Children’s abilities in different age groups were compared using the analysis of variance (ANOVA), Scheffe test, the Kruskal-Wallis test, and the post-hoc test. The differences between the total scores of the two genders were also determined using the Mann-Whitney U test. Results: Comparing the prelinguistic skills in different age groups indicated a statistically significant increase in the scores as children grow up. Children with a positive family history of speech-language disorders scored lower on the checklist than the others (91.03±17.37). Furthermore, there were statistically significant differences between the two genders in developing gesture, vocalization, first words, social interaction, imitation, and play; girls had higher scores.  Conclusion: Based on the studies conducted in different countries, prelinguistic skills develop as children grow up; these skills facilitate language acquisition and other social skills. The present study also demonstrated the development of these skills alongside children’s development. This similarity between Persian-speaking children and other children from different cultures and languages, as well as better performance in children with a negative family history of speech-language impairments, confirm the role of genetic factors in children’s development. Moreover, the differences in the development of some prelinguistic skills between girls and boys reveal the impact of various factors, such as social factors, on prelinguistic skills development

Selecting chemotherapy schedules for adjuvant treatment of early stage breast cancer, what is the rationale behind?

Breast cancer is one of the most prevalent cancers that oncologists are faced with in their clinics. The varieties of clinical features of the disease result to very different scenarios in the processes of treatment decision making. While classic factors of stage, grade, age and hormone receptor status are still the criterion for choosing treatment, a very delicate list of other prognostic and predictive factors have been entered to this field over recent two decades. The evidence-based medicine rules to treat patients based on the best evidences that have been found by powered randomized clinical trials. Different panels and guidelines gathering these evidences try to help oncologists to find the best treatment methods through the variable and sometimes contradicting results. As it is always the main objective, increasing the survival rates in addition to the ideal aim of curing the disease is usually the target.  Finding the best and the most practical chemotherapy regimen against breast cancer needs to notice the biology of this disease and its varieties along with each individual patient condition. It is clear that not all patients need the most complicated and expensive treatment

Quality and quantity of bone at intraoral graft donor sites in type 2 diabetic patients versus healthy controls: A cone-beam computed tomography study

Objectives: This study aimed to compare the quality and quantity of bone at intraoral autogenous graft donor sites in type II diabetes mellitus (DM) patients versus healthy controls using cone-beam computed tomography (CBCT).&nbsp;Materials and methods: This case-control study was conducted on CBCT scans of 50 DM patients and 50 healthy controls between 20-70 years. Maximum height, width, length, and volume of harvestable bone at the symphysis, ramus, palate, and tuberosity were measured bilaterally. The Hounsfield unit (HU) was also calculated to assess bone quality. The two groups were compared regarding the quality and quantity of harvestable bone using an independent t-test. The effect of confounders was analyzed by the regression model (alpha = 0.05).&nbsp;Results: DM patients had significantly lower harvestable bone volume at the symphysis, ramus, and tuberosity than healthy controls (p &lt; 0.001) but this difference was not significant at the palate (p = 0.957). Also, bone quality was significantly lower at the symphysis, ramus, palate, and tuberosity in DM patients (p &lt; 0.001).&nbsp;Conclusion: Diabetic patients had significantly lower bone quality and quantity at intraoral graft donor sites than healthy controls. Mandibular symphysis had higher bone volume and density than ramus, palate, and tuberosity for graft harvesting in diabetic patients

Optimal Scheduling of Reconfigurable Microgrids in Both Grid-Connected and Isolated Modes Considering the Uncertainty of DERs

In this study, an operation strategy is introduced for distributed energy resources (DERs) in reconfigurable microgrids (MGs) to improve voltage profiles, minimize power losses, and boost the system performance. The proposed methodology aims to minimize power loss and energy not supplied (ENS) in MGs with an intelligent share of DERs and network reconfiguration in grid-connected and islanded modes. Due to the inherent uncertain nature of renewable DERs, these sources’ power output is considered as an uncertain parameter, and its effect on the system characteristics is analyzed. The state-of-the-art information gap decision theory (IGDT) approach is utilized to explore different decision-making strategies in the energy scheduling of reconfigurable MGs to deal with such uncertainty. To validate the effectiveness of the proposed method, the IEEE 33-bus radial system is utilized as the test MG. The simulation results show the importance of energy storage systems and reconfiguration in dealing with uncertainty and improving system reliability

Polarography Can Successfully Quantify Heavy Metals in Dentistry

Background and Objectives: Due to the nutritional and behavioral patterns of children, their teeth can be a good indicator of heavy metal uptake from over the years. To determine the amount of Zn, Cu, Cd, and Pb accumulated in the body, primary teeth of children in Zanjan, Iran, were examined with a polarography device. Materials and Methods: Samples were collected from dentistry clinics of Zanjan, Iran, and were prepared for acid digestion, and then were analyzed by a polarography device for determining the concentration of lead, copper, zinc, and cadmium. Results: Data were analyzed by a t-independent test to compare different groups (p < 0.05). Based on the results obtained from this study, the mean concentrations of zinc, lead, copper, and cadmium were 245, 7.66, 5.33, and 0.0879 µg/g, respectively, which shows that the amount of each of the four elements was more than the amounts that have been reported for different countries. The results showed no significant difference between age, tooth type, and jaw groups. Conclusions: We conclude that primary teeth are an important biological indicator to evaluate the concentration of heavy elements in the human body. The high concentrations of these elements in the primary teeth analyzed in this study could be attributed to the high concentrations of these elements in the environment of Zanjan.Dentistry, Faculty ofNon UBCReviewedFacultyResearche