Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity

The identification of agents that can reverse drug resistance in cancer chemotherapy, and enhance the overall efficacy is of great interest. Paclitaxel (PTX) belongs to taxane family that exerts an antitumor effect by stabilizing microtubules and inhibiting cell cycle progression. However, PTX resistance often develops in tumors due to the overexpression of drug transporters and tumor-promoting pathways. Noncoding RNAs (ncRNAs) are modulators of many processes in cancer cells, such as apoptosis, migration, differentiation, and angiogenesis. In the present study, we summarize the effects of ncRNAs on PTX chemotherapy. MicroRNAs (miRNAs) can have opposite effects on PTX resistance (stimulation or inhibition) via influencing YES1, SK2, MRP1, and STAT3. Moreover, miRNAs modulate the growth and migration rates of tumor cells in regulating PTX efficacy. PIWI-interacting RNAs, small interfering RNAs, and short-hairpin RNAs are other members of ncRNAs regulating PTX sensitivity of cancer cells. Long noncoding RNAs (LncRNAs) are similar to miRNAs and can modulate PTX resistance/sensitivity by their influence on miRNAs and drug efflux transport. The cytotoxicity of PTX against tumor cells can also be affected by circular RNAs (circRNAs) and limitation is that oncogenic circRNAs have been emphasized and experiments should also focus on onco-suppressor circRNAs. © 2022 Wiley Periodicals LLC

Ewing's Sarcoma of Mandible: Practical Approach to a Challenging Case

As a rare entity, sarcomas of the head and neck are challenging cases. In this paper, we represent a unique case of Ewing sarcoma of mandible, serving as an example of multidisciplinary team importance in a developing country. © 2022 Case Reports in Ophthalmology. All rights reserved

Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles

Glycogen synthase kinase-3 beta (GSK-3β) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer's. In this study, using computational methods, flavonoid compounds were investigated for potential inhibitors against GSK-3β. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3β receptor constructed by homology modeling. Best binding poses were discovered via in silico molecular docking simulation. We surveyed noncovalent interactions among amino acid residues involved in the active site of the modeled Protein and compounds via molecular docking and molecular dynamics (MD). Moreover, ADMET characteristics of best docking conformers have been investigated. The obtained results revealed that compound 1 containing chromenone moiety with binding energy H-bond �11.4 kcal/mol inhibited effectively binding pocket of the GSK-3β receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3β receptor remained stable throughout 100 ns MD simulation, and also analysis of ADMET profiles revealed that selected compounds had good drug-likeness and pharmacokinetic properties. Hence, it was suggested that compounds with chromenone scaffold could potentially inhibit GSK-3β. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3β inhibitors. © 2022 The Author

Role of microRNAs in tumor progression among Iranian population: An overview

Cancer is one of the main health challenges in the world with a noticeable global mortality rate. It has been reported that there is a rising trend of cancer incidence among Iranians during the recent decades. Various factors are associated with tumorigenesis such as environment, genetic, and epigenetic. Epigenetic is heritable transcriptional changes without DNA alterations which are exerted through DNA methylation, chromatin modifications, and noncoding RNA profiles. Aberrant epigenetic changes are commonly observed in early stages of neoplastic transformation. Since majority of cancer related deaths are related to the late diagnosis and lack of an efficient early detection method, it is required to introduce novel early detection methods. MicroRNAs are secreted into the body fluids and are stable for a long-term storage. Therefore, stability and easy detection in body fluids makes microRNAs as ideal and less invasive biomarkers of early detection in cancer. In present review we summarized all of the significant reported miRNAs in different tumor types until now among Iranian population to pave the way for introducing a general population based non coding panel of markers for the early detection of cancers in this population. © 2022 Elsevier B.V

Comparison Between Hesperidin, Coumarin, and Deferoxamine Iron Chelation and Antioxidant Activity Against Excessive Iron in the Iron Overloaded Mice

Objective: Iron accumulation in the brain leads to the development of Alzheimer�s and Parkinson�s diseases. Nowadays, iron chelation therapy is the best way to decrease the side effects of iron and amyloid plaques accumulation. Iron chelators are commonly used for the treatment of Alzheimer�s disease. Previous studies have shown that natural products such as phenol and flavonoid compounds could chelate heavy metals. In the current study, we examined the iron chelation activity of hesperidin and coumarin on the brain tissue of iron-overloaded mice. Methods: 48 NMRI male mice were divided into eight groups (n = 6). Six groups were treated with iron dextran (100 mg/kg/day) four times a week for 6 weeks. After stopping the injections for a month, five groups of iron-overloaded mice were treated with hesperidin, coumarin, and desferal four times a week subsequent for four subsequent weeks. Finally, the mice were anesthetized, and blood samples were collected from the ventricle of the heart for subsequent examination. The brain tissues were isolated and fixed in the 4 paraformaldehyde solution for Perl�s staining. Results: The results show that hesperidin and coumarin could strongly chelate excessive iron from the serum and deposit iron from the brain tissue compared to desferal group. Catalase and super oxidase activity were decreased in the iron-overloaded group, but in the treated group by hesperidin and coumarin, the enzyme�s activity was increased significantly. Conclusion: Hesperidin and coumarin, as natural products, are powerful options to chelate iron ions and increase the activity of antioxidant enzymes. Copyright © 2022 Aalikhani, Safdari, Jahanshahi, Alikhani and Khalili

Naringin is a promising natural compound for therapy of iron-overload disorders

Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. is being used Therefore, we provided 35 mice were classified into and they were divided into 5 five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then threated with normal saline (as control), naringin or DFO (n=7). Group A treated by normal saline, the others treated with iron dextran. After that group A and B treated with normal slaine, group C received desferal, group D and E received high and low dose of naringin respectively. Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl�s staining.after The results revealed that naringin is more potent thant DFO in removing excessive iron ions deposited in liver tissues, indicating indication that naringin is a promising natural compound for therapy of iron overload disorders. © 2022, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved

Development of an online cancer data collection and processing tool for population-based cancer registries in a low-resource setting: The CanDCap experience from Golestan, Iran

Background: Golestan Population-based Cancer Registry (GPCR) with more than 15-years experiences developed an in-house online software called Cancer Data Collection and Processing (CanDCap) to improve its data collection operations from the conventional offline method to new online method. We aimed to report the methods and framework that GPCR applied to design and implementation of the CanDCap. Methods: CanDCap was designed based on International Agency for Research on Cancer (IARC) protocols and standards and according to the GPCR workflow. CanDCap has two parts including a web-based online part for data collection and a windows-based part for data processing consisting of quality control and deduplication of repeated records. Questionnaire for User Interface Satisfaction (QUIS) was used in order to assess user interaction satisfaction. Results: CanDCap was implemented in 2018 and could improve the quality of the GPCR data during its first three years of activity (2018�2020), during which about 9,000 records were registered. The coverage for optional items including national ID, father name, address and telephone number were improved from 23 , 32 , 83 and 82 in conventional offline method (2015�2017) to 83 , 81 , 87 , and 90 after using the CanDCap (2018�2020), respectively. The timeliness was also improved from 4 years to 2 years. Overall, user interaction satisfaction was acceptable (7.8 out of 9). Conclusion: CanDCap could resulted in improvement in data quality and timeliness of the GPCR as a cancer registry unit with limited resources. It has the potential to be considered as a model for population-based cancer registries in lower-resource settings. © 2022 Elsevier B.V

3-Dimensional Model to Study Apoptosis Induction of Activated Natural Killer Cells Conditioned Medium Using Patient-Derived Colorectal Cancer Organoids

Natural killer (NK) cells are innate lymphocytes that can kill tumor cells via different pathways, including the secretion of cytotoxic granules in immunological synapses and the binding of apoptosis-inducing ligands with cognate death receptors on tumor cells. These ligands are also soluble in NK cells conditioned medium (NK-CM). However, novel preclinical in vitro models are required for solid tumors such as colorectal cancer (CRC) to investigate apoptosis induction of activated NK-CM in a tissue-like structure. In the present study, we established a patient-derived CRC organoid culture system as a new tool for CRC research in the last decade. Tumor organoids were stained with hematoxylin and eosin (H&E) and compared with the original tumor taken from the patient. Goblet cell differentiation and mucus secretion were evaluated using periodic acid�Schiff and alcian blue histochemical staining. Moreover, tumor organoids were stained for CDX2 and Ki67 markers with immunohistochemistry (IHC) to investigate gastrointestinal origin and proliferation. Histopathological evaluations indicated tumor organoids represent patient tumor characteristics. Primary NK cells were isolated and characterized using CD56 marker expression and the lack of the CD3 marker. Flow cytometry results showed the purity of isolated CD3�and CD56 + NK cells about 93. After further ex vivo expansion, IL-2-activated NK-CM was collected. Secretions of IFN-γ and TNF-α were measured to characterize activated NK-CM. Cytokines levels were significantly elevated in comparison to the control group. Soluble forms of apoptosis-inducing ligands, including TNF-related apoptosis-inducing ligand (TRAIL) and FasL, were detected by western blot assay. Colon cancer organoids were treated by IL-2-activated NK-CM. Apoptosis was assessed by Annexin V-FITC/PI staining and quantified by flow cytometry. In conclusion, despite the activated NK-CM containing apoptosis-inducing ligands, these ligands� soluble forms failed to induce apoptosis in patient-derived colon cancer organoids. Nevertheless, we report a reliable in vitro assessment platform in a personalized setting. Copyright © 2022 Parseh, Khosravi, Fazel, Ai, Ebrahimi-Barough, Verdi and Shahbazi

Mental Health and Resilience in Emergency Medical Services Practitioners During the COVID-19 Pandemic

Background: The prevalence of the Coronavirus disease 2019 (COVID-19) pandemic, as one of the biggest global health threats, has had psychological impacts on healthcare workers (HCWs) and all aspects of their mental health, particularly resilience. Objectives: This study aimed to investigate the relationship between mental health and resilience in prehospital emergency medical services (EMS) practitioners. Methods: This descriptive/analytical cross-sectional study was conducted in 2020 using a web-based questionnaire, wherein the data were collected from a total number of 115 EMS practitioners working in 115 EMS stations in Golestan province, northern Iran, selected using convenience sampling. The data collection tools were also the General Health Questionnaire-28 (score range: 0-84) and the Connor-Davidson Resilience Scale (score range: 0-100). The relationship between both questionnaires was then examined by structural equation modeling via maximum likelihood estimation. In addition, multiple linear regression (MLR) was applied to reflect on the factors affecting the resilience mean score. Results: The mental health and resilience mean scores in the EMS practitioners were 25.73 ± 8.90 and 72.25 ± 12.63, respectively. Furthermore, 43.5 and 49.6 of the subjects had good and mild mental health conditions, respectively. The correlation coefficient between both questionnaires (-0.51) revealed that mental health deterioration diminished resilience in the EMS practitioners. Additionally, the type of employment and mental health mean score had a significant effect on the resilience mean value (R2 in MLR = 0.54). Conclusions: The study results demonstrated that more than half of the EMS practitioners had moderate mental health status, and their resilience mean score was high. Therefore, it is suggested to evaluate the prevalence of other common types of mental problems, such as anxiety, depression, and sleep disorders, in HCWs during the COVID-19 pandemic at the national level in future studies. © 2022, Author(s)

Grief Experience After Deaths: Comparison of Covid-19 and non-Covid-19 Causes

The grief caused by loved ones� death causes grief is a global phenomenon. The Covid-19 pandemic caused significant changes in human lifestyles and the experience of grief. The purpose of the present study was to compare grief experiences in the deceased's relatives caused by Covid-19 and non-Covid-19. Seventy-five first- and second-degree relatives of the deceased infected with Covid-19 (n = 33) and non-Covid-19 (n = 42) in a Gorgan hospital in northern Iran were included cross-sectional study using convenience sampling. Data were collected using the GEQ-34 grief experience questionnaire and demographic variables and questions related to funeral and burial. The results revealed that the deceased's burial quality caused by the Covid-19 group was significantly lower (p = 0.035). However, the feeling of the Covid-19 label is significantly higher (p 0.05). Nevertheless, the experience of grief was significantly different in the group of relatives of the deceased infected by Covid-19 in terms of notoriety (P = 0.040) and physical reactions (p = 0.002). Educational interventions to reduce stigma and discrimination due to death caused by Covid-19 and clinical and psychological support of relatives of the deceased due to Covid-19 are recommended by compiling appropriate messages from different channels. © The Author(s) 2022