The role of cancer-associated fibroblasts and exosomal miRNAs-mediated intercellular communication in the tumor microenvironment and the biology of carcinogenesis: a systematic review.

CAFs (cancer-associated fibroblasts) are highly flexible cells of the cancer microenvironment. They produce the extracellular matrix (ECM) constituents that form the structure of the tumor stroma but are also a source of metabolites, growth factors, chemokines, and exosomes that impact every aspect of the tumor, including its response to treatment. It is believed that exosomal miRNAs facilitate intercellular signaling, which is essential for the development of cancer. The role of miRNAs and CAFs in the tumor microenvironment (TME) and carcinogenesis is reviewed in this paper. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines were used to perform a systematic review. Several databases, including Web of Science, Medline, Embase, Cochrane Library, and Scopus, were searched using the following keywords: CAFs, CAF, cancer-associated fibroblasts, stromal fibroblasts, miRNA, exosomal miRNAs, exosome and similar terms. We identified studies investigating exosomal miRNAs and CAFs in the TME and their role in carcinogenesis. A total of 12,572 papers were identified. After removing duplicates (n = 3803), 8774 articles were screened by title and abstract. Of these, 421 were excluded from further analysis. It has been reported that if exosomal miRNAs in CAFs are not functioning correctly, this may influence the secretory phenotype of tip cells and contribute to increased tumor invasiveness, tumor spread, decreased treatment efficacy, and a poorer prognosis. Under their influence, normal fibroblasts (NFs) are transformed into CAFs. Furthermore, they participate in metabolic reprogramming, which allows for fast proliferation of the cancer cell population, adaptation to growing energy demands, and the capacity to avoid immune system identification.

Medicinal Chemistry of Antisense Oligonucleotides for Therapeutic Use in SARS-CoV-2: Design Strategies and Challenges for Targeted Delivery.

BACKGROUND: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects. OBJECTIVE: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations. METHODS: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19. RESULTS: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics. CONCLUSION: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.

Enhanced adsorption and removal of Cd(II) from aqueous solution by amino-functionalized ZIF-8.

Zeolite imidazolate framework-8 (ZIF-8), which is a special subgroup of metal-organic frameworks (MOFs), was synthesized and modified by ethylenediamine (ZIF-8-EDA) to prepare an efficient adsorbent for the high sorption of Cd2+ ions from solution. The synthesized and modified ZIF-8 (ZIF-8-EDA) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET), field emission scanning electron microscopy (FE-SEM) with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) analysis. The optimum conditions for dosage of adsorbent, initial ion concentration, pH, and contact time were 0.05 g/l, 50 mg/l, 6, and 60 min, respectively, for cadmium ion sorption from aqueous solutions with a removal efficiency of 89.7% for ZIF-8 and 93.5% for ZIF-8-EDA. Adsorption kinetics and equilibrium data were analyzed using the Langmuir and Freundlich equations. The Langmuir model fitted the equilibrium data better than the Freundlich model. According to the Langmuir equation, the maximum uptake for the cadmium ions was 294.11(mg/g). The calculated thermodynamic parameters (ΔG°, ΔH°, and ΔS°) indicated that the adsorption process was feasible, spontaneous, and endothermic at 20-50 °C. Based on the results, the amino functionalized ZIF-8 had improved adsorption performance due to the replacing of the starting linker with organic ligands that had effective functional groups, leading to chemical coordination due to the interaction of metal ions with the non-bonding pair of electrons on the N atoms of the amino functional group. The selectivity toward metal ion adsorption by ZIF-8-EDA was Cd2+ > Pb2+ > Ni2+ .

A metaphorical advantage for bilingual children? Understanding figurative meaning by L2 and L3 EFL learners.

This study compared school-aged monolingual and bilingual English-as-a-foreign-language (EFL) learners in terms of understanding metaphors on recall, multiple-choice, and reasoning tasks. It also examined the relationship between cognitive capacity and understanding metaphors on different measures. A hundred and thirty Persian-Turkish early bilinguals and 122 monolingual Persian-speaking EFL learners took three different tests of metaphor comprehension and the Figural Intersections Test, a test of cognitive capacity. Bilinguals outperformed monolinguals in terms of cognitive capacity and understanding metaphors on two of the tasks, though with a small effect size. Furthermore, there was a significant positive relationship between cognitive capacity and the scores on the multiple-choice and reasoning tests, but not the recall test. Results suggest that bilingual L3 learners have an edge in understanding metaphors, reflecting a cognitive advantage.

LYZ2-SH3b as a novel and efficient enzybiotic against methicillin-resistant Staphylococcus aureus.

BACKGROUND: Enzybiotics are promising alternatives to conventional antibiotics for drug-resistant infections. Exolysins, as a class of enzybiotics, show antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). This study evaluated a novel exolysin containing an SH3b domain for its antibacterial activity against MRSA. METHODS: This study designed a chimeric exolysin by fusing the Cell-binding domain (SH3b) from Lysostaphin with the lytic domain (LYZ2) from the gp61 enzyme. Subsequently, LYZ2-SH3b was cloned and expressed in Escherichia coli (E. coli). Finally, the antibacterial effects of LYZ2-SH3b compared with LYZ2 and vancomycin against reference and clinical isolates of MRSA were measured using the disc diffusion method, the minimal inhibitory concentration (MIC), and the minimal bactericidal concentration (MBC) assays. RESULTS: Analysis of bioinformatics showed that LYZ2-SH3b was stable, soluble, and non-allergenic. Protein purification was performed with a 0.8 mg/ml yield for LYZ2-SH3b. The plate lysis assay results indicated that, at the same concentrations, LYZ2-SH3b has a more inhibitory effect than LYZ2. The MICs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239). This suggests a higher efficiency of LYZ2-SH3b compared to LYZ2. Furthermore, the MBCs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239), thus confirming the superior lytic activity of LYZ2-SH3b over LYZ2. CONCLUSIONS: The study suggests that phage endolysins, such as LYZ2-SH3b, may represent a promising new approach to treating MRSA infections, particularly in cases where antibiotic resistance is a concern. But further studies are needed.

COVID-19-associated acute pancreatitis: a systematic review of case reports.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) mainly involves the respiratory system but can also affect the digestive system and cause several gastrointestinal manifestations. Acute pancreatitis has been reported as one of the rare presentations of COVID-19. This study aimed to systematically review case reports on COVID-19-associated acute pancreatitis. METHODS: Publications were retrieved through a comprehensive search in four databases on October 1, 2021. Eligible ones that demonstrated the potential association of acute pancreatitis and COVID-19 were included for data extraction. RESULTS: After screening 855 citations, 82 articles containing 95 cases were included, and their data were extracted. The most common presentation was abdominal pain (88/95, 92.6%), followed by nausea/vomiting (61/95, 64.2%). Mortality was reported in 10.5% of cases. The initial presentation was acute pancreatitis, COVID-19, and concomitant in 32.6% (31/95), 48.4% (46/95), and 18.9% (18/95) of cases, respectively. Among the included cases, acute pancreatitis severity was associated with ICU admission, COVID-19 severity, and the outcome. Also, the initial presentation was associated with COVID-19 severity (P values ˂0.05). CONCLUSIONS: Current evidence indicates that acute pancreatitis can present before, after, or concomitant with COVID-19. Appropriate investigations should be performed in cases with suspicious clinical presentations. Longitudinal studies should address whether or not, there is a causative relationship between COVID-19 and acute pancreatitis.

High cardiac output state due to pelvic arterio-venous shunt: a case report and review of the literature.

We are presenting a 35-year-old woman with past medical history of disseminated leiomyomatosis who presented with heart failure symptoms and was found to have post-capillary pulmonary hypertension and high cardiac output state in right heart catheterization secondary to a huge pelvic arterio-venous fistula.

Revisiting Inhibition Effects of miR-28 as a Metastasis Suppressor in Gastrointestinal Cancers.

MicroRNAs are critical epigenetic regulators that can be used as diagnostic, prognostic, and therapeutic biomarkers for the treatment of various diseases, including gastrointestinal cancers, among a variety of cellular and molecular biomarkers. MiRNAs have also shown oncogenic or tumor suppressor roles in tumor tissue and other cell types. Studies showed that the dysregulation of miR-28 is involved in cell growth and metastasis of gastrointestinal cancers. MiR-28 plays a key role in controlling the physiological processes of cancer cells including growth and proliferation, migration, invasion, apoptosis, and metastasis. Therefore, miR-28 expression patterns can be used to distinguish patient subgroups. Based on the previous studies, miR-28 expression can be a suitable biomarker to detect tumor size and predict histological grade metastasis. In this review, we summarize the inhibitory effects of miR-28 as a metastasis suppressor in gastrointestinal cancers. miR-28 plays a role as a tumor suppressor in gastrointestinal cancers by regulating cancer cell growth, cell differentiation, angiogenesis, and metastasis. As a result, using it as a prognostic, diagnostic, and therapeutic biomarker in the treatment of gastrointestinal cancers can be a way to solve the problems in this field.

Overview of the cardio-metabolic impact of the COVID-19 pandemic.

Evidence has shown that cardiometabolic disorders (CMDs) are amongst the top contributors to COVID-19 infection morbidity and mortality. The reciprocal impact of COVID-19 infection and the most common CMDs, the risk factors for poor composite outcome among patients with one or several underlying diseases, the effect of common medical management on CMDs and their safety in the context of acute COVID-19 infection are reviewed. Later on, the changes brought by the COVID-19 pandemic quarantine on the general population's lifestyle (diet, exercise patterns) and metabolic health, acute cardiac complications of different COVID-19 vaccines and the effect of CMDs on the vaccine efficacy are discussed. Our review identified that the incidence of COVID-19 infection is higher among patients with underlying CMDs such as hypertension, diabetes, obesity and cardiovascular disease. Also, CMDs increase the risk of COVID-19 infection progression to severe disease phenotypes (e.g. hospital and/or ICU admission, use of mechanical ventilation). Lifestyle modification during COVID-19 era had a great impact on inducing and worsening of CMDs. Finally, the lower efficacy of COVID-19 vaccines was found in patients with metabolic disease.

A Review on Advanced CRISPR-Based Genome-Editing Tools: Base Editing and Prime Editing.

In the field of medicine, it is axiomatic that the need of a precise gene-editing tool is critical to employ therapeutic approaches toward pathogenic mutations, occurring in human genome. Today we know that most of genetic defects are caused by single-base pair substitutions in genomic DNA. The ability to make practically any targeted substitutions of DNA sequences at specified regions in the human genome gives us the chance to employ gene therapy in most known diseases associated with genetic variants. In this regard, CRISPR/Cas9 applications is becoming more and more popular along with the significant advancements of life sciences, by employing this technology in genome-editing and high-throughput screenings. Several CRISPR/Cas-based mammalian cell gene-editing techniques have been developed during the last decade, including nucleases, base editors, and prime editors, all of which have the exact mechanism at first glance. However, they address a subset of known pathogenic sequence mutations using different methods. First, we highlight the development of CRISPR-based gene-editing tools. Then we describe their functions and summarize the conducted research studies, which are increasing the reliability of these strategies to better efficiencies for prospective gene therapies in the near future. Lastly, we compare the capabilities of all these platforms together besides their probable limitations.

Are all types of empathy associated with lower aggression in athletes? A cross-sectional study on Iranian athletes.

BACKGROUND: This study aimed to evaluate the association between cognitive and affective empathy and aggression in a sample of Iranian athletes. METHODS: We designed a cross-sectional study. The participants were selected by multistage random sampling among six colleges in Tehran, Iran's capital. We used the interpersonal reactivity index (IRI) to evaluate empathy, and Reactive Proactive Aggression Questionnaire, and the Buss-Perry aggression questionnaire to evaluate aggression. RESULTS: In total, 492 athletes with a mean age of 27.42 years (SD = 7.72) participated in the study, of which 298 (60.6%) were male, and 194 (39.4%) were female. IRI's fantasy and personal distress subscales scores were positively associated with proactive and reactive aggression scores (p < 0.05). The score of the perspective-taking subscale of IRI was negatively associated with proactive and reactive aggression scores (p < 0.05). The score of the empathic concern subscale of IRI had a negative association with the proactive aggression score (p < 0.001). The score of the perspective-taking subscale of IRI had negative associations with all Buss-Perry aggression questionnaire subscales' scores (p < 0.05). The score of the personal distress subscale of IRI had positive associations with all Buss-Perry aggression questionnaire subscales' scores (p < 0.05), except with the verbal aggression subscale score. The score of the fantasy subscale of IRI was positively associated with the score of the hostility subscale of the Buss-Perry questionnaire (p = 0.001). CONCLUSION: Perspective-taking is negatively associated with all kinds of aggression in athletes. Future studies can be conducted to determine the possible role of perspective-taking in preventive aggression, which can be a target for interventions. On the other hand, the score of the personal distress subscale of IRI is positively associated with all types of aggression scores, indicating that not all types of empathy inhibit aggression in athletes.

E-cigarette aerosol impairs male mouse skeletal muscle force development and prevents recovery from injury.

To date, there has been a lag between the rise in E-cigarette use and an understanding of the long-term health effects. Inhalation of E-cigarette aerosol delivers high doses of nicotine, raises systemic cytokine levels, and compromises cardiopulmonary function. The consequences for muscle function have not been thoroughly investigated. The present study tests the hypothesis that exposure to nicotine-containing aerosol impairs locomotor muscle function, limits exercise tolerance, and interferes with muscle repair in male mice. Nicotine-containing aerosol reduced the maximal force produced by the extensor digitorum longus (EDL) by 30%-40% and, the speed achieved in treadmill running by 8%. Nicotine aerosol exposure also decreased adrenal and increased plasma epinephrine and norepinephrine levels, and these changes in catecholamines manifested as increased muscle and liver glycogen stores. In nicotine aerosol exposed mice, muscle regenerating from overuse injury only recovered force to 80% of noninjured levels. However, the structure of neuromuscular junctions (NMJs) was not affected by e-cigarette aerosols. Interestingly, the vehicle used to dissolve nicotine in these vaping devices, polyethylene glycol (PG) and vegetable glycerin (VG), decreased running speed by 11% and prevented full recovery from a lengthening contraction protocol (LCP) injury. In both types of aerosol exposures, cardiac left ventricular systolic function was preserved, but left ventricular myocardial relaxation was altered. These data suggest that E-cigarette use may have a negative impact on muscle force and regeneration due to compromised glucose metabolism and contractile function in male mice.NEW & NOTEWORTHY In male mice, nicotine-containing E-cigarette aerosol compromises muscle contractile function, regeneration from injury, and whole body running speeds. The vehicle used to deliver nicotine, propylene glycol, and vegetable glycerin, also reduces running speed and impairs the restoration of muscle function in injured muscle. However, the predominant effects of nicotine in this inhaled aerosol are evident in altered catecholamine levels, increased glycogen content, decreased running capacity, and impaired recovery of force following an overuse injury.

Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets.

Over the past few years, the cancer-related disease has had a high mortality rate and incidence worldwide, despite clinical advances in cancer treatment. The drugs used for cancer therapy, have high side effects in addition to the high cost. Subsequently, to reduce these side effects, many studies have suggested the use of natural bioactive compounds. Among these, which have recently attracted the attention of many researchers, quercetin has such properties. Quercetin, a plant flavonoid found in fresh fruits, vegetables and citrus fruits, has anti-cancer properties by inhibiting tumor proliferation, invasion, and tumor metastasis. Several studies have demonstrated the anti-cancer mechanism of quercetin, and these mechanisms are controlled through several signalling pathways within the cancer cell. Pathways involved in this process include apoptotic, p53, NF-κB, MAPK, JAK/STAT, PI3K/AKT, and Wnt/ß-catenin pathways. In addition to regulating these pathways, quercetin controls the activity of oncogenic and tumor suppressor ncRNAs. Therefore, in this comprehensive review, we summarized the regulation of these signalling pathways by quercetin. The modulatory role of quercetin in the expression of various miRNAs has also been discussed. Understanding the basic anti-cancer mechanisms of these herbal compounds can help prevent and manage many types of cancer.

Targeted therapy in Coronavirus disease 2019 (COVID-19): Implication from cell and gene therapy to immunotherapy and vaccine.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19.

Design, synthesis, and characterization of a novel Zn(II)-2-phenyl benzimidazole framework for the removal of organic dyes.

A novel Zn (II) organic framework comprising 2-phenyl benzimidazole (ZPBIF-1) was synthesized by using a solvothermal method. The characterization of the synthesized MOF was performed utilizing XRD, SEM, FT-IR, 1H-NMR, 13C-NMR, MS, XPS, TG/DTA, and N2 sorption analysis. ZPBIF-1 was successfully utilized to remove Acid red 88, Basic Violet 14, Basic Blue 54, and Congo red dyes in aqueous solutions. In this study, some parameters, including adsorbent dosage, initial dye concentration, contact time, temperature, and pH, were examined. To evaluate the experimental data, Freundlich, Langmuir, Temkin, and Dubinin-Radushkevich isotherm models were used. In this case, Langmuir is the most suitable model. Several kinetic models, including First-order, pseudo-first-order, second-order, and Pseudo-second-order kinetic models, Elovich's, and Weber's intraparticle diffusion models, were utilized to comprehend the detailed adsorption process. According to the pseudo-second-order kinetic model, dye sorption kinetics is best described. In addition, thermodynamic parameters like enthalpy (ΔH°), Gibbs free energy (ΔG°), and entropy (ΔS°) were also achieved and analyzed. The experimental studies thus suggest that Zn (II) metal-organic framework based on 2-phenyl benzimidazole could be a promising candidate for eliminating dyes from aqueous solution. Hence, the experimental studies suggest that a Zn (II) metal-organic framework based on 2-phenylbenzimidazole could be a promising candidate for eliminating dyes from aqueous solution. The maximum adsorption capacity of ZPBIF-1 was 1666.66, 1250, 1000, and 1250 mg/g for Acid red 88, Basic violet 14, Basic blue 54, and Congo red dyes, respectively. Furthermore, this method was used to remove contaminant dyes from textile wastewater, and an acceptable result was obtained.

B-Cell Epitope Mapping from Eight Antigens of Candida albicans to Design a Novel Diagnostic Kit: An Immunoinformatics Approach.

Invasive candidiasis is an emerging fungal infection and a leading cause of morbidity in health care facilities. Despite advances in antifungal therapy, increased antifungal drug resistance in Candida albicans has enhanced patient fatality. The most common method for Candida albicans diagnosing is blood culture, which has low sensitivity. Therefore, there is an urgent need to establish a valid diagnostic method. Our study aimed to use the bioinformatics approach to design a diagnostic kit for detecting Candida albicans with high sensitivity and specificity. Eight antigenic proteins of Candida albicans (HYR1, HWP1, ECE1, ALS, EAP1, SAP1, BGL2, and MET6) were selected. Next, a construct containing different immunodominant B-cell epitopes was derived from the antigens and connected using a suitable linker. Different properties of the final construct, such as physicochemical properties, were evaluated. Moreover, the designed construct underwent 3D modeling, reverse translation, and codon optimization. The results confirmed that the designed construct could identify Candida albicans with high sensitivity and specificity in serum samples of patients with invasive candidiasis. However, experimental studies are needed for final confirmation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10989-022-10413-1.

Vulvovaginal candidiasis: An overview of mycological, clinical, and immunological aspects.

AIM: To provide an overview of clinical, immunological, and mycological aspects of vulvovaginal candidiasis (VVC). METHODS: A literature search was conducted to find relevant articles about different aspects of VVC. Related data from retrieved articles were summarized in different headings. RESULTS: VVC has a global distribution and Candida albicans is the leading cause of infection except for specific patient groups like postmenopausal, diabetic, or immunocompromised women. VVC has a range of clinical presentations, accordingly, its diagnosis should be based on clinical examination coupled with laboratory investigations. The best therapeutic regimen depends on the patient's conditions and the causative agent. Moreover, factors like drug resistance of the causative agents and different mutations in the immunity-related genes could affect the treatment outcome. CONCLUSION: As a globally distributed disease, VVC needs further attention, especially in areas related to the treatment failure and recurrence of the disease.

Evaluation of exosomal non-coding RNAs in cancer using high-throughput sequencing.

Clinical oncologists need more reliable and non-invasive diagnostic and prognostic biomarkers to follow-up cancer patients. However, the existing biomarkers are often invasive and costly, emphasizing the need for the development of biomarkers to provide convenient and precise detection. Extracellular vesicles especially exosomes have recently been the focus of translational research to develop non-invasive and reliable biomarkers for several diseases such as cancers, suggesting as a valuable source of tumor markers. Exosomes are nano-sized extracellular vesicles secreted by various living cells that can be found in all body fluids including serum, urine, saliva, cerebrospinal fluid, and ascites. Different molecular and genetic contents of their origin such as nucleic acids, proteins, lipids, and glycans in a stable form make exosomes a promising approach for various cancers' diagnoses, prediction, and follow-up in a minimally invasive manner. Since exosomes are used by cancer cells for intercellular communication, they play a critical role in the disease process, highlighting the importance of their use as clinically relevant biomarkers. However, regardless of the advantages that exosome-based diagnostics have, they suffer from problems regarding their isolation, detection, and characterization of their contents. This study reviews the history and biogenesis of exosomes and discusses non-coding RNAs (ncRNAs) and their potential as tumor markers in different types of cancer, with a focus on next generation sequencing (NGS) as a detection method. Moreover, the advantages and challenges associated with exosome-based diagnostics are also presented.

Comparison of vaccine hesitancy during the low and high points of COVID-19 in a population under international sanctions: A longitudinal mixed-methods study in Iran.

Introduction: Along with the challenges of COVID-19 vaccine supply in low-income countries, vaccine hesitancy was another problem for the health system. The aim of this study was to deeply understand the challenges of vaccine acceptance, the vaccination process, and to compare the affecting vaccine acceptance in the high and low points of the epidemic in Iran. Methods: In the qualitative part of this mixed-methods study, content analysis was used to investigate experiences and perceptions about COVID-19 vaccination in four groups. In the quantitative study, in March 2021 (low point), and on August 1, 2021 (high point), two population-based cross-sectional studies were performed in Tehran and its rural, with sample sizes of 1,200 and 1,872 people aged over 18 years, respectively. Multinomial (polytomous) logistic regression was used to determine the factors affecting hesitation and unwillingness to receive the vaccine. Results: Disbelief in vaccine safety, vaccine distrust, ignorance and confusion, and inadequate facilities were the common reasons extracted in the two qualitative studies. At the low and high points of the epidemic, vaccine acceptance was 83.6% (95% CI: 81.3-85.9) and 65.8% (95% CI: 65.8-71.0), respectively. Residence in rural areas, (Odds Ratio: 0.44, p = 0.001), being a student (Odds Ratio: 0.41, p = 0.011), housewives (Odds Ratio: 0.63, p = 0.033), illiteracy (Odds Ratio: 4.44, p = 0.001), and having an underlying disease (Odds Ratio: 4.44, p = 0.001) were factors affecting on vaccine acceptance. Discussion: Counter-intuitively, acceptance did not increase at the peak of epidemic. The presence of obstacles, such as increased distrust in the effectiveness of vaccines due to the occurrence of multiple peaks in different vaccinated countries, as well as the influence of the media, anti-vaccine campaigns, and lack of proper communication about risks caused more hesitation. More investigation to understand how people accept or reject vaccine and its long term consequences is recommended.