Xanthohumol hinders invasion and cell cycle progression in cancer cells through targeting MMP2, MMP9, FAK and P53 genes in three-dimensional breast and lung cancer cells culture.

BACKGROUND: Despite recent advances in the treatment of lung and breast cancer, the mortality with these two types of cancer is high. Xanthohumol (XN) is known as a bioactive compound that shows an anticancer effect on cancer cells. Here, we intended to investigate the anticancer effects of XN on the breast and lung cancer cell lines, using the three-dimensional (3D) cell culture. METHODS: XN was isolated from Humulus lupulus using Preparative-Thin Layer Chromatography (P-TLC) method and its authenticity was documented through Fourier Transform Infrared spectroscopy (FT-IR) and Hydrogen Nuclear Magnetic Resonance (H-NMR) methods. The spheroids of the breast (MCF-7) and lung (A549) cancer cell lines were prepared by the Hanging Drop (HD) method. Subsequently, the IC50s of XN were determined using the MTT assay in 2D and 3D cultures. Apoptosis was evaluated by Annexin V/PI flow cytometry and NFκB1/2, BAX, BCL2, and SURVIVIN expressions. Cell cycle progression was determined by P21, and P53 expressions as well as PI flow cytometry assays. Multidrug resistance was investigated through examining the expression of MDR1 and ABCG2. The invasion was examined by MMP2, MMP9, and FAK expression and F-actin labeling with Phalloidin-iFluor. RESULTS: While the IC50s for the XN treatment were 1.9 µM and 4.74 µM in 2D cultures, these values were 12.37 µM and 31.17 µM in 3D cultures of MCF-7 and A549 cells, respectively. XN induced apoptosis in MCF-7 and A549 cell lines. Furthermore, XN treatment reduced cell cycle progression, multidrug resistance, and invasion at the molecular and/or cellular levels. CONCLUSIONS: According to our results of XN treatment in 3D conditions, this bioactive compound can be introduced as an adjuvant anti-cancer agent for breast and lung cancer.

The effects of Abemaciclib on cell cycle and apoptosis regulation in anaplastic thyroid cancer cells.

BACKGROUND: Anaplastic thyroid cancer (ATC) is an aggressive subtype of thyroid cancer, accounting for 1 to 2% of all cases. Deregulations of cell cycle regulatory genes including cyclins, cyclin-dependent kinases (CDKs), and endogenous inhibitors of CDKs (CKIs) are hallmarks of cancer cells and hence, studies indicate the inhibition of CDK4/6 kinases and cell cycle progression as potent therapeutic strategies. In this study, we investigated the anti-tumor activity of Abemaciclib, a CDK4 and CDK6 inhibitor, in ATC cell lines. METHODS AND RESULTS: The ATC cell lines C643 and SW1736 were selected to study the antiproliferative effects of Abemaciclib using a cell proliferation assay and crystal violet staining assay. Annexin V/PI staining and cell cycle analysis by flow cytometry were also performed to examine the effects on apoptosis induction and cell cycle arrest. Wound healing assay and zymography analysis examined the effects of the drug on invasive abilities of ATC cells and Western blot analyses were applied to further study the anti-tumor mechanism of Abemaciclib, in addition to combination treatment with alpelisib. Our data demonstrated that Abemaciclib significantly inhibited cell proliferation and increased cellular apoptosis and cell cycle arrest in ATC cell lines, while considerably reducing cell migration and colony formation. The mechanism seemed to involve the PI3K pathway. CONCLUSION: Our preclinical data highlight CDK4/6 as interesting therapeutic targets in ATC and suggest CDK4/6-blockade therapies as promising strategies in this malignancy.

Molecular evidence reveals thyrotropin intervention enhances the risk of developing radioiodine-refractory differentiated thyroid carcinoma.

Radioiodine (RAI) is the mainstay of treatment for differentiated thyroid carcinoma (DTC) following total thyroidectomy. Nevertheless, about 5% of patients with DTC are RAI-refractory (RAI-R). Understanding the molecular mechanisms associated with DTC during progression towards RAI-R DTC, including thyroid-stimulating hormone levels, may help to explain the pathophysiology of challenging RAI-R DTC clinical cases.

BI-847325, a selective dual MEK and Aurora kinases inhibitor, reduces aggressive behavior of anaplastic thyroid carcinoma on an in vitro three-dimensional culture.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the most aggressive subtype of thyroid cancer. In this study, we used a three-dimensional in vitro system to evaluate the effect of a dual MEK/Aurora kinase inhibitor, BI-847325 anticancer drug, on several cellular and molecular processes involved in cancer progression. METHODS: Human ATC cell lines, C643 and SW1736, were grown in alginate hydrogel and treated with IC50 values of BI-847325. The effect of BI-847325 on inhibition of kinases function of MEK1/2 and Aurora kinase B (AURKB) was evaluated via Western blot analysis of phospho-ERK1/2 and phospho-Histone H3 levels. Sodium/iodide symporter (NIS) and thyroglobulin (Tg), as two thyroid-specific differentiation markers, were measured by qRT-PCR as well as flow cytometry and immunoradiometric assay. Apoptosis was assessed by Annexin V/PI flow cytometry and BIM, NFκB1, and NFκB2 expressions. Cell cycle distribution and proliferation were determined via P16, AURKA, and AURKB expressions as well as PI and CFSE flow cytometry assays. Multidrug resistance was evaluated by examining the expression of MDR1 and MRP1. Angiogenesis and invasion were investigated by VEGF expression and F-actin labeling with Alexa Fluor 549 Phalloidin. RESULTS: Western blot results showed that BI-847325 inhibits MEK1/2 and AURKB functions by decreasing phospho-ERK1/2 and phospho-Histone H3 levels. BI-847325 induced thyroid differentiation markers and apoptosis in ATC cell lines. Inversely, BI-847325 intervention decreased multidrug resistance, cell cycle progression, proliferation, angiogenesis, and invasion at the molecular and/or cellular levels. CONCLUSION: The results of the present study suggest that BI-857,325 might be an effective multi-targeted anticancer drug for ATC treatment.

A systematic review on thyroid organoid models: time-trend and its achievements.

Current in vitro models have played important roles in improving knowledge and understanding of cellular and molecular biology, but cannot exactly recapitulate the physiology of human tissues such as thyroid. In this article, we conducted a systematic review to present scientific and methodological time-trends of the reconstruction and generation of 3 D functional thyroid follicles and organoids for thyroid research in health and disease. "Web of Science (ISI)", "Scopus", "Embase", "Cochrane Library", and "PubMed" were systematically searched for papers published since 1950 to May 2020 in English language, using the predefined keywords. 212 articles were reviewed and finally 28 papers that met the inclusion and exclusion criteria were selected. Among the evidence for the examination of 3 D cell culture methods in thyroid research, there were only a few studies related to the organoid technology and its potential applications in understanding morphological, histological, and physiological characteristics of the thyroid gland and reconstructing this tissue. Besides, there was no study using organoids to investigate the tumorigenesis process of thyroid. Based on the results of this study, despite all the limitations and controversies, the exciting and promising organoid technology offers researchers a wide range of potential applications for more accurate modeling of thyroid in health and diseases and provides an excellent preclinical in vitro platform. In future, organoid technology can provide a better understanding of the molecular mechanisms of pathogenesis and tumorigenesis of thyroid tissue and more effective treatment for related disorders due to more accurate simulation of the thyroid physiology.

Molecular mechanisms of long non-coding RNAs in anaplastic thyroid cancer: a systematic review.

BACKGROUND: anaplastic thyroid cancer (ATC) is one of the most lethal and aggressive cancers. Evidence has shown that the tumorigenesis of ATC is a multistep process involving the accumulation of genetic and epigenetic changes. Several studies have suggested that long non-coding RNAs (lncRNAs) may play an important role in the development and progression of ATC. In this article, we have collected the published reports about the role of lncRNAs in ATC. METHODS: "Scopus", "Web of Science", "PubMed", "Embase", etc. were systematically searched for articles published since 1990 to 2020 in English language, using the predefined keywords. RESULTS: 961 papers were reviewed and finally 33 papers which fulfilled the inclusion and exclusion criteria were selected. Based on this systematic review, among a lot of evidences on examining the function of lncRNAs in thyroid cancer, there are only a small number of studies about the role of lncRNAs and their molecular mechanisms in the pathogenesis of ATC. CONCLUSIONS: lncRNAs play a crucial role in regulation of different processes involved in the development and progression of ATC. Currently, just a few lncRNAs have been identified in ATC that may serve as prognosis markers such as GAS5, MIR22HG, and CASC2. Also, because of the dysregulation of Klhl14-AS, HOTAIRM1, and PCA3 during ATC development and progression, they may act as therapeutic targets. However, for most lncRNAs, only a single experiment has evaluated the expression profile in ATC tissues/cells. Therefore, further functional studies and expression profiling is needed to resolve this limitation and identify novel and valid biomarkers.

Investigation of promoter methylation of FSCN1 gene and FSCN1 protein expression in differentiated thyroid carcinomas.

FSCN1 gene encodes an actin-bundling protein, FSCN1, which is involved in formation of actin-based structures that contribute to cell migration. High levels of FSCN1 expression is observed in cells with extended membranes and protrusions. Moreover, up-regulation of FSCN1 has been reported in several epithelial carcinomas. Therefore, FSCN1 is thought to play a role in cell movement and invasion. However, the mechanism behind FSCN1 up-regulation is not known. We investigated the expression of FSCN1 using immunohistochemistry. Methylation-specific PCR was adopted to analyze the methylation status of FSCN1 promoter as a potential regulatory mechanism in FSCN1 expression. The samples included papillary thyroid carcinoma, follicular thyroid carcinoma and goiter samples (controls). Methylation of FSCN1 promoter was observed in 50% of follicular, 48.6% of papillary and 60% of controls. The promoter was unmethylated in 16.7% of follicular samples, 5.7% of papillary samples and 26.7% of controls. In the remaining 33.3% of follicular and 45.7% of papillary samples as well as 13.3% of controls, both methylated and unmethylated alleles were amplified, a condition referred to as semi-methylation. The results showed that FSCN1 promoter was significantly hypomethylated in papillary cases while the methylation status was not significantly altered in follicular cases. On the other hand, FSCN1 was expressed in only nine papillary samples. Regarding protein expression and methylation status, we suggest that hypomethylation of FSCN1 promoter in papillary thyroid carcinoma does not lead to overexpression of FSCN1 and that there might be other regulatory mechanisms involved in FSCN1 up-regulation.

Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer.

Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid cancers. Resistance to current therapies is still a challenge. MicroRNAs are a class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR that is overexpressed in nearly all cancers including ATC. Accumulating evidence suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle progression, and differentiation. Therefore, we evaluated the application of Off-miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR-21). PTEN gene expression was performed as a known target of miR-21. Stemness state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene expression and flow cytometry. Sodium/iodide symporter (NIS) and thyroglobulin (TG) were measured as ATC differentiation markers. In addition, cell cycle progression was investigated via the alterations of p21 gene expression and flow cytometry. Specific downregulation of miR-21 induced the differentiation and apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state and cell cycle progression. Knockdown of miR-21 significantly increased the expression of PDCD4, p21, NIS, and TG while leading to decreased expression of Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an oncomiR, has a role not only in stemness state but also in tumor growth, differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way for ATC therapy.

Efficacy of the hatching event in assessing the embryo toxicity of the nano-sized TiO2 particles in zebrafish: a comparison between two different classes of hatching-derived variables.

The aim of the present study was to evaluate the nano-TiO2 toxicity to zebrafish embryos through evaluating the success in hatching in relationship with hours post-exposure instead of considering just the total hatching rate. Zebrafish embryos 4h post-fertilization were exposed to nTiO2 (0, 0.01, 10, and 1000 µg mL(-1)) for 130 h. The hatching rate (HR) was calculated for each concentration (treatment). The HR magnitude was significantly (p<0.001) correlated (using simple regression) to hours post-exposure time interval (hpe; 34, 58, 82, 106, and 130), noted as HR.hpe. The HR descriptive statistics (HRds) and the parameters of the regression models (i.e., constant, x, F, and r(2)) were recruited to define 15 HRds- and 4 h.hpe-derived variables, respectively. The efficacy of the variables was evaluated. Exposure to nTiO2 led to a significant: premature hatching and general decrease in time required for normal hatching; and change in HR and hpe interrelations in a dose-dependent manner. The major change in hatchability between the treatment and control occurred at 58 hpe (62 hpf), when the treatment with nTiO2 induced significant premature hatching compared to only 6% of the hatched embryos in the control at the same time point. EC10 and EC50 values that cause premature hatching at 58 hpe for nTiO2 are 0.073 µg mL(-1) and 107.2 µg mL(-1) respectively. In general(,) this study shows multivariate differences among exposure concentrations of nTiO2 recruiting hatching-derived endpoints.

Design and implementation of a national quality registry of thyroid cancer in Iran: study protocol.

Purpose: Thyroid cancer is recognized as the predominant form of endocrine cancer. The likelihood of cancer recurrence and the development of distant metastases varies depending on the cancer's pathology and stage. Iran currently lacks country-specific data on thyroid cancer, which can potentially result in clinicians deviating from the optimal treatment. The primary objectives of establishing such a registry are to determine the incidence, identify risk factors, and evaluate treatment outcomes for thyroid cancer within the Iranian population. Ultimately, the overarching goal of this protocol study is to reduce mortality and morbidity rates among thyroid cancer patients by implementing appropriate interventions based on the findings derived from this registration system. Methods: The study will enroll all individuals aged 18 years and older who have received a diagnosis of primary thyroid carcinoma based on pathology criteria. Data will be collected from various thyroid clinic centers. The participating centers include the Endocrinology Clinic at Shariati Hospital, the Thyroid Clinic in the Nuclear Medicine Center at Shariati Hospital, as well as pathology and nuclear medicine centers in Kerman and Bushehr. Patient records comprise information on outpatient visits to the clinic. Conclusion: The registry aims to enhance treatment approaches and follow-up protocols while serving as a foundation for conducting clinical, epidemiological, and basic science studies based on robust evidence-based data.

Decoding the expression pattern of MUC3A in gastric adenocarcinoma: unveiling the key to successful immunotherapy.

AIMS: Despite the promise of immunotherapy for gastric adenocarcinoma, resistance is common, necessitating the validation of new targets. Based on our previous bioinformatics analysis, the MUC3A antigen emerged as a promising candidate for immunotherapy against gastric adenocarcinoma. However, a comprehensive understanding of its expression at protein level remains elusive, despite its crucial role in determining clinical response. We also sought to establish a connection between the expression pattern and relevant clinical variables of the disease, whenever feasible. METHODS: Immunohistochemistry was used to determine the percentage of MUC3A-positive tumor cells in primary (PT) and metastatic tumor (MT) sites of 190 gastric adenocarcinoma patients. We also evaluated the association between MUC3A expression and variables such as Lauren classification, history of neoadjuvant chemotherapy and/or radiotherapy, and overall patient survival. RESULTS: Median MUC3A expression was 50% in PT and 70% in MT sites, exhibiting a positive correlation. MT intestinal type showed significantly higher MUC3A expression compared to other types. Neoadjuvant therapy history did not affect MUC3A expression. Higher MUC3A expression correlated with improved survival. CONCLUSIONS: Based on our previous bioinformatics data and the consistently high expression of MUC3A on gastric tumor cells, we propose advancing experimental aspects of anti-MUC3A immunotherapy for gastric adenocarcinoma.

Illuminating the role of lncRNAs ROR and MALAT1 in cancer stemness state of anaplastic thyroid cancer: An exploratory study.

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans that accounts for a considerable rate of cancer-associated mortality. Since conventional therapies are lacking sufficient efficacy, new treatment approaches are required. This goal could be achieved through a better understanding of the molecular pathogenesis of ATC. Thyroid tumorigenesis is initiated by a subpopulation of cells known as cancer stem cells (CSCs) with specific markers such as CD133 that confers to processes such as self-renewal and metastasis. Besides, some long non-coding RNAs (lncRNAs) promote tumorigenesis by mediating the aforementioned processes. Methods: Here, we designed an exploratory study to investigate the role of lncRNAs ROR and MALAT1 and their related genes in CSC stemness. Using magnetic-activated cell sorting (MACS), the CD133- and CD133+ subpopulations were separated in SW1736 and C643 ATC cell lines. Next, the expression profiles of the CD133 marker, MALAT1, and its associated genes (CCND1, NESTIN, MYBL2, MCL1, IQGAP1), as well as ROR and its related genes (POU5F1, SOX2, NANOG), were explored by qRT-PCR. Results: We found significant up-regulation of ROR, POU5F1, SOX2, NANOG, CD133, MALAT1, IQGAP1, and MCL1 in CD133+ SW1736 cells compared to CD133- cells. As for CD133+ C643 cells, CCND1, IQGAP1, POU5F1, SOX2, NANOG, and NESTIN were significantly up-regulated compared to CD133- cells. Conclusions: This study suggests that these lncRNAs in CD133-positive SW1736 and C643 cells might regulate stemness behaviors in ATC.

Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 µM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 µM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 µM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 µM) and 8a (IC50 = 12.96 µM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 µM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

Management goal achievements of diabetes care in Iran: study profile and main findings of DiaCare survey.

Aim: This paper presented the methodology and main findings of a population-based survey to determine diabetes care status among type 2 diabetic subjects in Iran. The current study assessed treatment goal achievements in type 2 diabetics, diabetes care service utilization, prevalence of diabetes complications, and psychological effects of diabetes in a representative sample of Iranian population in urban and rural areas. Materials and Methods: This nationwide study was conducted between 2018 and 2020 as the observational survey entitled "Diabetes Care (DiaCare)". We studied a representative sample of participants with type 2 diabetes, aged 35-75 years, living in urban and rural areas in all thirty- one provinces of Iran. Data were collected by an interviewer in a form of a questionnaire that includes demographic and socioeconomic status, family and drug history, lifestyle, and self-reported psychological status according to a Patient's Health Questionnaire (PHQ). Management goal achievements, diabetes care service utilization, diabetes complications and psychological effects of diabetes were also assessed. Physical measurements were measured based on standard protocol. Fasting blood glucose (FBG), HbA1c, lipid profile, and also urine albumin to creatinine ratio were obtained from all participants of the study. Results: Overall, 13,334 people with type 2 diabetes in 31 provinces of Iran completed the survey (response rate: 99.6%). In total 13,321 participants, 6683(50.17%) women and 6638(49.83%) men were included in our analysis. Thirteen recruited patients refused after the consenting process and did not respond. The mean age (SD) of total participants was 54.86 ± 9.44 years and 71.50% were from the urban areas. 13.66% of diabetic patients had achieved the triple target of management [controlled HbA1c, blood pressure, and Low-Density Lipoprotein-Cholesterol (LDL-C)] in the whole country. While 28.74% of people had controlled HbA1c and 33.40% of them had controlled FBG. Diabetic subjects living in rural areas had less controlled HbA1c (23.93 vs. 29.48), controlled FBG (29.50 vs. 34.20) and controlled triple targets (10.45 vs. 14.32) than those living in urban areas. Diabetic neuropathy and diabetic foot were more common in women than men, while end-stage of renal disease (ESRD) was more common in men than women. Conclusions: This population-based study provided representative information about diabetes care in Iran. The high prevalence of diabetes and low proportion of diabetes control in Iran implies that it is necessary to identify factors associated with poor treatment goal achievements. Besides, general improvements in management and care of diabetes are mandatory.

Prevalence of thyroid dysfunction among Iranian older adults: a cross-sectional study.

There is limited data on the prevalence of thyroid dysfunction in the older population. This study aimed to determine the prevalence of thyroid dysfunction among a sample of Iranian older adults. A cross-sectional analysis of older adults who aged 60 years and over was conducted. A total of 363 subjects were randomly selected from Birjand longitudinal aging study (BLAS) cohort study. Serum thyroid-stimulating hormone (TSH) level, total thyroxine (T4) and total triiodothyronine (T3) were measured by the enzyme-linked immunosorbent assay (ELISA). Based on thyroid function tests and history of taking medicines used to treat thyroid disorders, participants were classified into the following groups: euthyroid, overt/subclinical hypothyroidism, and overt/subclinical hyperthyroidism. Subsequently, the crude and World Health Organization (WHO) age-standardized prevalence were estimated for different thyroid function categories. A total of 171 men and 192 women, aged 60-94 years, were randomly selected. The crude prevalence of total hypothyroidism was 22.31% (subclinical [18.46%], overt [3.86%]), and that of hyperthyroidism was 1.66% (subclinical [1.38%], overt [0.28%]). The crude prevalence of total thyroid dysfunction was, therefore, 23.97%. A female preponderance was noticed in both total (P-value = 0.035) and overt (P-value = 0.035) hypothyroidism. An increasing trend with age was noticed in the prevalence of total hypothyroidism (P-value = 0.049). Age-standardized prevalence of total hypothyroidism and hyperthyroidism was 26.63% (95% confidence interval [CI] 20.58-33.69%) and 1.11% (95% CI 0.49-2.51%), respectively. A considerable proportion of our study population demonstrated evidence of thyroid dysfunction, particularly subclinical hypothyroidism. Our findings highlight the importance of further investigation of thyroid disorders among older Iranian adults.

Association of survivin gene polymorphism with endometrial cancer.

OBJECTIVE: Survivin is an inhibitor of apoptosis protein, which is up-regulated in endometrial cancer (EC). A promoter region polymorphism (-31G/C) in the survivin gene has been reported as a modulator of gene expression. The aim of this study was to explore the frequency of survivin -31G/C polymorphism in tumor tissues from patients with EC in an Iranian population compared to that of healthy controls. MATERIALS AND METHODS: Paraffin-embedded tissue sections from patients diagnosed with EC (n = 31) and healthy controls (n = 30) were examined. Genotyping for survivin -31G/C polymorphism was performed using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: The presence of allele C was found to be significantly increased in EC tissues compared to the healthy tissues (GG vs GC + CC, P = 0. 01; OR, 3.6; 95% CI, 1.1-11.9). CONCLUSION: Our data are in keeping with a previous finding regarding the role of survivin gene polymorphism in malignancies. This finding highlights the role of survivin in pathogenesis of various carcinomas, which might have therapeutic implications.

Recent advances in gene therapy-based cancer monotherapy and synergistic bimodal therapy using upconversion nanoparticles: Structural and biological aspects.

In accordance with human genetics and genomics advances over the past years, it can be found that cancer is created through a somatic aberration in the host genome. Accordingly, researchers use therapeutic methods in genetic manipulation to discover the possible cure for the disease. In combination with traditional cancer treatments, gene therapy (GT) is essential in future cancer therapy. The development of powerful nanocarriers for targeted, controlled, and efficient intracellular delivery of therapeutic biomolecules that increase pharmacokinetics indicates that the development of GT is highly dependent on nanotechnology. Among nanocarriers, upconversion nanoparticles (UCNPs) have become the focus of great attention in the realm of inorganic nanomedicines following the strategy of "diagnosis for treatment" due to their outstanding features including safety, deep penetration of near-infrared (NIR) light into tissue, and reduction of unfavorable side effects of NIR-triggered therapies. Moreover, various individual therapies can be intelligently combined into a single nanotranostic system based on a UCNP platform for multimodal synergistic treatment. Given that the preparation of multifunctional nanomaterials is a prerequisite for the realization of cancer treatment, especially synergistic therapies, the recognition of the main components of advanced nanoparticles can help researchers in choosing the proper platform for cancer treatment. In view of this, the main goal of this review is to highlight the latest advances in the construction and application of upconversion nanoparticles as carriers for gene delivery and gene editing in cancer monotherapy and bimodal synergistic therapy, with an emphasis on the structural and biological aspects of these studies.

Development of a Multiepitope Vaccine Against SARS-CoV-2: Immunoinformatics Study.

Background: Since the first appearance of SARS-CoV-2 in China in December 2019, the world witnessed the emergence of the SARS-CoV-2 outbreak. Due to the high transmissibility rate of the virus, there is an urgent need to design and develop vaccines against SARS-CoV-2 to prevent more cases affected by the virus. Objective: A computational approach is proposed for vaccine design against the SARS-CoV-2 spike (S) protein, as the key target for neutralizing antibodies, and envelope (E) protein, which contains a conserved sequence feature. Methods: We used previously reported epitopes of S protein detected experimentally and further identified a collection of predicted B-cell and major histocompatibility (MHC) class II-restricted T-cell epitopes derived from E proteins with an identical match to SARS-CoV-2 E protein. Results: The in silico design of our candidate vaccine against the S and E proteins of SARS-CoV-2 demonstrated a high affinity to MHC class II molecules and effective results in immune response simulations. Conclusions: Based on the results of this study, the multiepitope vaccine designed against the S and E proteins of SARS-CoV-2 may be considered as a new, safe, and efficient approach to combatting the COVID-19 pandemic.

Establishment of biobank facility at Endocrinology and Metabolism Research Institute of Iran: experiences, challenges, and future outlook.

Biobanking as an emerging procedure referring to the development of sample storage technologies which provide essential structures for conducting research. This paper presents the experiences and challenges faced while establishing the non-communicable diseases (NCDs)-dedicated biobank at Endocrinology and Metabolism Research Institute (EMRI) in Iran, such as infrastructure, Laboratory Information Management System (LIMS), ethical and legal aspects, sample collection, preservation, and quality control (QC). NCDs are a major health problem around the world and in Iran, which is access to biological samples are required to understanding and planning to these diseases. The main objectives of the EMRI biobank is currently the collection and storage of biological samples such as blood, serum, plasma, urine and DNA from patients with NCDs including diabetes mellitus osteoporosis and elderly population based on cohort and cross-sectional studies. The biobank of EMRI aims to have a major impact on the NCDs by supplying biological samples for national and international research projects.

Alginate-based 3D cell culture technique to evaluate the half-maximal inhibitory concentration: an in vitro model of anticancer drug study for anaplastic thyroid carcinoma.

BACKGROUND: Three-dimensional (3D) cell culture methods are identified for simulating the biological microenvironment and demonstrating more similarity to in vivo circumstances. Anaplastic thyroid carcinoma (ATC) is a lethal endocrine malignancy. Despite different treatment approaches, no improvement in the survival rate of the patients has been shown. In this study, we used the 3D in vitro ATC model to investigate the cytotoxic effect of BI-847325 anticancer drug in two-dimensional (2D)- and 3D- cultured cells. METHODS: Human ATC cell lines, C643 and SW1736, were cultured in one percentage (w/v) sodium alginate. Spheroids were incubated in medium for one week. The reproducibility of the fabrication of alginate beads was evaluated. Encapsulation of the cells in alginate was examined by DAPI (4',6-diamidino-2-phenylindole) staining. Survival of alginate-encapsulated cells was evaluated by CFSE (5,6-Carboxyfluorescein N-hydroxysuccinimidyl ester) staining. The population doubling times of C643 and SW1736 cell lines cultured in 2D monolayer as well as in 3D system were calculated. The cytotoxic effect of BI-847325 on 2D- and 3D- cultured cell lines was assessed for 24-72 h by MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide] assay. Finally, the 3D culture results were compared with the 2D culture method. RESULTS: The half-maximal inhibitory concentration (IC50) values of BI-847325 were higher in 3D culture compared to 2D culture. The cytotoxicity data indicated that 3D in vitro models were more resistant to chemotherapy agents. CONCLUSIONS: The findings of this study are beneficial for developing in vitro ATC 3D models to analyze the efficacy of different chemotherapy drugs and formulations.