A qualitative report on experiences of participants in the young innovative leadership program.

BACKGROUND: Leadership in health system is a universal challenge. The Young Innovative Leadership Program (YILP) designed for undergraduate and postgraduate medical sciences students, implemented at the Isfahan University of Medical Sciences, aimed to cultivate leadership capacities through a 16-week training program. This program comprises ten modules covering innovation, change leadership, and management skills, with mentor-facilitated group discussions. This study aimed to provide a qualitative report of the experiences of participants in the YILP. METHODS: A qualitative study was conducted in 2022, three months after the end of the training program, to investigate the participants' perspectives. Data was extracted through in-depth, semi-structured interviews with 14 participants. RESULTS: In this study 14 undergraduate and postgraduate medical sciences students who had participated in the YILP the previous year were included. Four main categories emerged from the interviews: "emergence of new horizons", "values as beacon", "an expanded toolbox", and "program's structure: a learning atmosphere". CONCLUSIONS: The results of our study indicated that medical science students would benefit from leadership development programs. In this regard, the framework utilized to implement YILP could serve as a role model.

The Cytotoxicity of 27-Hydroxycholesterol in MCF-7 and MDA-MB-231.

Background: Although several roles of 27-hydroxycholesterol (27-HC), the most abundant oxysterol in blood circulation, in cancers have been elucidated, its impact on breast cancer proliferation and its pathway remain unknown. Materials and Methods: The effect of 27-HC on breast cancer cell proliferation and its pathway was evaluated using Michigan Cancer Foundation - 7 (MCF-7) and M.D. Anderson - Metastatic Breast 231 (MDA-MB-231) cell lines. The MTT assay was applied after 24- and 48-hour incubation to distinguish cell proliferation. To determine the cause of different viability results from the MTT assay, the Annexin-FITC/PI test was used at concentrations of 0.1, 1, and 10 µM after 24- and 48-hour incubation. Results: 27-HC in concentrations of 5, 10, and 20 µM induced cell cytotoxicity compared with control. Also, the annexin V conjugated with fluorescein isothiocyanate/propidium iodide (Annexin-FITC/PI) test revealed an increase in total apoptotic cells treated with 0.1, 1, and 10 µM of 27-HC after 48 hours (P value < 0.05). Besides, the cytotoxic effect of 27-HC was observed at 10 µM concentration in both cell lines, MCF-7 and MDA-MB-231 (P value < 0.05). Conclusion: The identification of 27-HC's cytotoxic effects on both estrogen receptor (ER)-negative and ER-positive breast cancer cell lines is a novel discovery that may be linked to LXRß.

The nexus of natural killer cells and melanoma tumor microenvironment: crosstalk, chemotherapeutic potential, and innovative NK cell-based therapeutic strategies.

The metastasis of melanoma cells to regional lymph nodes and distant sites is an important contributor to cancer-related morbidity and mortality among patients with melanoma. This intricate process entails dynamic interactions involving tumor cells, cellular constituents, and non-cellular elements within the microenvironment. Moreover, both microenvironmental and systemic factors regulate the metastatic progression. Central to immunosurveillance for tumor cells are natural killer (NK) cells, prominent effectors of the innate immune system with potent antitumor and antimetastatic capabilities. Recognizing their pivotal role, contemporary immunotherapeutic strategies are actively integrating NK cells to combat metastatic tumors. Thus, a meticulous exploration of the interplay between metastatic melanoma and NK cells along the metastatic cascade is important. Given the critical involvement of NK cells within the melanoma tumor microenvironment, this comprehensive review illuminates the intricate relationship between components of the melanoma tumor microenvironment and NK cells, delineating their multifaceted roles. By shedding light on these critical aspects, this review advocates for a deeper understanding of NK cell dynamics within the melanoma context, driving forward transformative strategies to combat this cancer.

Microfluidic-based technologies in cancer liquid biopsy: Unveiling the role of horizontal gene transfer (HGT) materials.

Liquid biopsy includes the isolating and analysis of non-solid biological samples enables us to find new ways for molecular profiling, prognostic assessment, and better therapeutic decision-making in cancer patients. Despite the conventional theory of tumor development, a non-vertical transmission of DNA has been reported among cancer cells and between cancer and normal cells. The phenomenon referred to as horizontal gene transfer (HGT) has the ability to amplify the advancement of tumors by disseminating genes that encode molecules conferring benefits to the survival or metastasis of cancer cells. Currently, common liquid biopsy approaches include the analysis of extracellular vesicles (EVs) and tumor-free DNA (tfDNA) derived from primary tumors and their metastatic sites, which are well-known HGT mediators in cancer cells. Current technological and molecular advances expedited the high-throughput and high-sensitive HGT materials analyses by using new technologies, such as microfluidics in liquid biopsies. This review delves into the convergence of microfluidic-based technologies and the investigation of Horizontal Gene Transfer (HGT) materials in cancer liquid biopsy. The integration of microfluidics offers unprecedented advantages such as high sensitivity, rapid analysis, and the ability to analyze rare cell populations. These attributes are instrumental in detecting and characterizing CTCs, circulating nucleic acids, and EVs, which are carriers of genetic cargo that could potentially undergo HGT. The phenomenon of HGT in cancer has raised intriguing questions about its role in driving genomic diversity and acquired drug resistance. By leveraging microfluidic platforms, researchers have been able to capture and analyze individual cells or genetic material with enhanced precision, shedding light on the potential transfer of genetic material between cancer cells and surrounding stromal cells. Furthermore, the application of microfluidics in single-cell sequencing has enabled the elucidation of the genetic changes associated with HGT events, providing insights into the evolution of tumor genomes. This review also discusses the challenges and opportunities in studying HGT materials using microfluidic-based technologies. In conclusion, microfluidic-based technologies have significantly advanced the field of cancer liquid biopsy, enabling the sensitive and accurate detection of HGT materials. As the understanding of HGT's role in tumor evolution and therapy resistance continues to evolve, the synergistic integration of microfluidics and HGT research promises to provide valuable insights into cancer biology, with potential implications for precision oncology and therapeutic strategies.

Comparative Analysis and Identification of Spike Mutations in Iranian COVID-19 Samples from the First Three Waves of Disease.

Background: The spike surface glycoprotein of SARS-CoV-2 is the essential protein in virus attachment to the target cell and cell entrance. As this protein contains immunodominant epitopes and is the main target for immune recognition, it is the critical target for vaccine and therapeutics development. In the current research, we analyzed the variability and mutations of the spike glycoprotein isolated from 72 COVID-19-positive patients from Iran's first three waves of disease. Materials and Methods: The RNA was extracted from nasopharyngeal samples of confirmed COVID-19 cases and served as a template for cDNA synthesis and reverse transcriptase polymerase chain reaction. The reverse transcriptase polymerase chain reaction products of each sample were assembled and sequenced. Results: After analysis of 72 sequences, we obtained 46 single nucleotide polymorphisms, including 23 that produce amino acid changes. Our analysis showed that the most frequent mutation was the D614G (in the samples of the second and third waves). Conclusions: Our findings suggest that developing effective vaccines requires identifying the predominant variants of SARS-CoV-2 in each community.

Remdesivir Prescription in Pregnant Women Infected with COVID-19: A Report of Compassionate Use.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease that the physiological changes in pregnancy can make pregnant patients more susceptible to more severe forms of this infection. Hence, the treatment of COVID-19 in pregnant women can be challenging. This study was designed to evaluate the safety and efficacy of Remdesivir in pregnant women with COVID-19. Materials and Methods: This study was conducted on 150 pregnant women with moderate to severe COVID-19 infection. Remdesivir was prescribed and continued for 5 or 10 days according to the patient's condition. Maternal and pregnancy outcomes and also recovery rates were evaluated. Moreover, additional variables were examined: age, gestational age, symptoms, O2 saturation and laboratory tests at admission, the interval between symptom initiation and admission to hospital and Remdesivir prescription, hospitalization days, and ICU admission. Results: The mean age was 32.37 years. Cough and dyspnea were the most prevalent symptoms (74% and 68.7%, respectively). At the time of admission, 79 (52.7%) women needed low-flow oxygen support, 67 (44.7%) needed high-flow oxygen support, and 4 (2.7%) were intubated. Fifty-four (36%) patients required ICU care. In patients who died (12 women), Remdesivir was prescribed later than those discharged (P value, 0.04). Patients with favorable pregnancy outcomes received Remdesivir earlier than those with unfavorable pregnancy outcomes (P value: 0.008). The recovery rate was 70% (89.9% in the low-flow oxygen, 50.7% in the NIPPV/high flow oxygen, and 0% in the intubated women). Conclusion: The results suggest that the early prescription of Remdesivir in pregnant women with moderate COVID-19 can improve the outcomes.

Effects of the Co-Administration of Morphine and Lipopolysaccharide on Toll-Like Receptor-4/Nuclear Factor Kappa ß Signaling Pathway of MDA-MB-231 Breast Cancer Cells.

Background: The Toll-like receptor 4 (TLR4) gene promotes migration in adenocarcinoma cells. Morphine is an agonist for TLR4 that has a dual role in cancer development. The promoter or inhibitor role of morphine in cancer progression remains controversial. This study aims to evaluate the effects of morphine on the TLR4, myeloid differentiation primary response protein 88-dependent (MyD88), and nuclear factor-kappa B (NF-κB) expressions in the human MDA-MB-231 breast cancer cell line. Materials and Methods: The cells were examined after 24 hours of incubation with morphine using the Boyden chamber system. TLR4, MyD88, and NF-κB mRNA expressions were assessed using quantitative real-time polymerase chain reaction (RT-PCR). The concentration of interleukin-2 beta was also measured using the ELISA assay. Results: According to the findings, three doses of morphine (0.25, 1.25, and 0.025 µM) increased the expression of the TLR4 and NF-κB genes, whereas no significant change was observed in the mRNA expression of MyD88. Furthermore, treatment with morphine and lipopolysaccharide (LPS) significantly decreased the expression of TLR4, MyD88, and NF-κB. However, no significant change was observed in interleukin 2 beta concentration. Conclusions: These findings confirmed the excitatory effects of morphine on TRL4 expression and the MYD88 signaling pathway in vitro.

Preclinical in vivo assessment of a cell-free multi-layered scaffold prepared by 3D printing and electrospinning for small-diameter blood vessel tissue engineering in a canine model.

Tissue-engineered vascular grafts (TEVGs) are promising alternatives to existing prosthetic grafts. The objective of this study is to evaluate the clinical feasibility of a novel multi-layered small-diameter vascular graft that has a hierarchical structure. Vascular grafts with elaborately designed composition and architecture were prepared by 3D printing and electrospinning and were implanted into the femoral artery of 5 dogs. The patency of the grafts was assessed using Doppler ultrasonography. After 6 months, the grafts were retrieved and histological and SEM examinations were conducted. During implantation, the grafts exhibited resistance to kinking and no blood seepage thanks to the helical structure of the innermost and outermost layers. The grafts showed a high patency rate and remodelling ability. At 6 months post-implantation, the lumen was endothelialized and middle layers were regenerated by infiltration of smooth muscle cells (SMCs) and deposition of extracellular matrix (ECM). These results suggest that the multi-layered vascular graft may be a promising candidate for small-diameter blood vessel tissue engineering in clinical practice.

The molecular perspective on the melanoma and genome engineering of T-cells in targeting therapy.

Melanoma, an aggressive malignant tumor originating from melanocytes in humans, is on the rise globally, with limited non-surgical treatment options available. Recent advances in understanding the molecular and cellular mechanisms underlying immune escape, tumorigenesis, drug resistance, and cancer metastasis have paved the way for innovative therapeutic strategies. Combination therapy targeting multiple pathways simultaneously has been shown to be promising in treating melanoma, eliciting favorable responses in most melanoma patients. CAR T-cells, engineered to overcome the limitations of human leukocyte antigen (HLA)-dependent tumor cell detection associated with T-cell receptors, offer an alternative approach. By genetically modifying apheresis-collected allogeneic or autologous T-cells to express chimeric antigen receptors, CAR T-cells can appreciate antigens on cell surfaces independently of major histocompatibility complex (MHC), providing a significant cancer cell detection advantage. However, identifying the most effective target antigen is the initial step, as it helps mitigate the risk of toxicity due to "on-target, off-tumor" and establishes a targeted therapeutic strategy. Furthermore, evaluating signaling pathways and critical molecules involved in melanoma pathogenesis remains insufficient. This study emphasizes the novel approaches of CAR T-cell immunoediting and presents new insights into the molecular signaling pathways associated with melanoma.

Steroid in the Treatment of Outpatient COVID-19: A Multicenter Randomized Controlled Trial.

Background: Early treatment of COVID-19 patients could reduce hospitalization and death. The effect of corticosteroids in the outpatient setting is still unknown. This study aimed to determine the effect of corticosteroids in the prevention of hospitalization of nonsevere cases. Materials and Methods: This study is a multicenter randomized controlled trial. Seventy five nonsevere COVID-19 patients presented between days 7 and 14 of their symptoms received either prednisolone or placebo. The primary outcome was hospitalization. The study protocol was registered in the Iranian Registry of Clinical Trials on December 2, 2020 (IRCT20171219037964N2). Results: Although the rate of hospitalization in the prednisolone group was higher than the placebo group (10.8% vs. 7.9%, respectively), it was not statistically significant (P value.,6). One patient in each group reported an adverse event and withdrew the medication. Conclusion: Considering the null effect of corticosteroids in the prevention of hospitalization in outpatient settings, it is suggested not to consider corticosteroids for outpatient treatment.

The Effect of Eight Weeks of Aquatic Exercises on Muscle Strength in Children with Cerebral Palsy: A Case Study.

Background: Cerebral palsy in children is considered a non-progressive brain injury due to abnormal brain development. The aim of this study was to investigate the effect of eight weeks of aquatic exercises on muscle strength in children with cerebral palsy. Materials and Methods: This study was performed on three boys with cerebral palsy with a mean age of 6.5 years. In this research, a single case study method with A1-B-A2 design has been used. After determining the position of the baseline, the intervention began and during 24 sessions of individual intervention, aquatic exercises were presented to the subjects and all three subjects were followed up for 2 consecutive weeks and one month after the end of the intervention. The strength of the flexor muscles of the arms and legs was measured by a power track dynamometer made by JTECK with a threshold of 4.4 N. Results: Based on the indicators of descriptive statistics and visual analysis, the intervention was effective for all three participants in muscle strength, and the strength of individuals after the intervention has improved compared to the baseline stage (percentage). Information overlap for the first and second participant in the strength of right thigh flexors was 75% and for the third participant was 100%. The strength of the upper and lower torso muscles improved after the end of the training compared to the basic stage. Conclusion: Aquatic exercises can increase the strength of children with cerebral palsy and provide a favorable environment for children with cerebral palsy.

A comprehensive review on novel targeted therapy methods and nanotechnology-based gene delivery systems in melanoma.

Melanoma, a malignant form of skin cancer, has been swiftly increasing in recent years. Although there have been significant advancements in clinical treatment underlying a well-understanding of melanoma-susceptible genes and the molecular basis of melanoma pathogenesis, the permanency of response to therapy is frequently constrained by the emergence of acquired resistance and systemic toxicity. Conventional therapies, including surgical resection, chemotherapy, radiotherapy, and immunotherapy, have already been used to treat melanoma and are dependent on the cancer stage. Nevertheless, ineffective side effects and the heterogeneity of tumors pose major obstacles to the therapeutic treatment of malignant melanoma through such strategies. In light of this, advanced therapies including nucleic acid therapies (ncRNA, aptamers), suicide gene therapies, and gene therapy using tumor suppressor genes, have lately gained immense attention in the field of cancer treatment. Furthermore, nanomedicine and targeted therapy based on gene editing tools have been applied to the treatment of melanoma as potential cancer treatment approaches nowadays. Indeed, nanovectors enable delivery of the therapeutic agents into the tumor sites by passive or active targeting, improving therapeutic efficiency and minimizing adverse effects. Accordingly, in this review, we summarized the recent findings related to novel targeted therapy methods as well as nanotechnology-based gene systems in melanoma. We also discussed current issues along with potential directions for future research, paving the way for the next-generation of melanoma treatments.

The Effects of 4-Week Aerobic Exercise on the Levels of CCl2, CCl5, and their Respective Receptors in Female BALB/C Mice Suffering from Breast Cancer.

Background: The studies reported that chemokines Chemokine (C-C motif) ligand 2 (CCL2) and Chemokine (C-C motif) ligand 5 (CCL5) have tumor-promoting roles in breast cancer (BC). The aim of the present study was to evaluate the effect of 4 weeks of continuous aerobic exercise (AE) on chemokines CCL2 and CCL5 and their relative receptors in animal model of human BC. Materials and Methods: BALB/c mice were divided randomly into four groups included cancer control (CC) and three other groups. The total duration of the experiment was 14 weeks, including 2 weeks of familiarization of mice with treadmills and three of 4-week periods of experiment. Tumor inoculation and formation were performed in the second 4-week period. Group 1 received AE in the first 4-week, Group 2 received AE in the second 4-week and Group 3 in the third 4-week. Results: The CCL2 was reduced significantly in Groups 1, 2, and 3 compared to control (F3,12= 4705, P = 0.0001). In terms of CCL5, a significant decrease was seen only between Group 3 and control. Western blot results showed a significant reduction in C-C chemokine receptor Type 2 (CCR2) between Group 1 versus CC and Group 2 versus CC (F3,20= 1.812, P = 0.004). In terms of C-C chemokine receptor Type 5 (CCR5) a significant decrease was observed between Group 2 versus control and Group 3 versus control (F3,20= 273.3, P = 0.042), (P = 0.004). Conclusion: It can be concluded that 4-week AE significantly reduces the chemokines CCL2 and CCL5 and their respective receptors levels CCR5 and CCR2 in different stages, and it may have an inhibitory effect on tumor growth.

SARS-CoV-2 Seroprevalence among Health-Care Workers in Isfahan, Iran.

Background: Health-care workers (HCWs) are in the frontline for fighting the coronavirus disease 2019 (COVID-19) pandemic and are at higher risk of acquiring the infection. Therefore, the defining immunity status among HCWs helps mitigate the exposure risk. In this study, we investigated the anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) and also the associated risk factors in the HCWs working in Isfahan University of Medical Sciences COVID-19 referral hospitals. Materials and Methods: In a cross-sectional study, demographics, COVID-19 symptoms during the past 2 weeks, and health-care details were collected from 200 consenting health workers of COVID-center-hospitals of Isfahan University of Medical Sciences from 23 October to 21 December 2020. The recombinant SARS-CoV2 nucleocapsid protein enzyme-linked immunosorbent assay-based IgM, and IgG antibody tests were evaluated. Data were analyzed using Chi-square and independent-t-student tests, and P < 0.05 was considered significant. Results: One hundred and forty-one women and 59 men with a mean age of 36.4 ± 7.77 years participated in the study. IgG Ab and IgM Ab were positive in 77 (38.5%) and 12 (6%) of samples, respectively, and both antibodies were detected in 9 (4.5%). Higher ages, direct contact with the patients with COVID-19, muscle pain, loss of taste and smell, fever, and cough were the factors associated with antibody seropositivity against SARS-CoV2. Conclusion: This study demonstrated that the prevalence of HCWs with antibodies against SARS-CoV-2 is relatively high in Isfahan University referral hospitals. The development of safety protocols and screening and vaccination strategies in the frontline HCWs must be implemented to reduce the burden of infection.

Corrigendum to "Hematological Inflammatory Markers in Patients with Clinically Confirmed Familial Hypercholesterolemia".

[This corrects the article DOI: 10.1155/2022/5051434.].

Smartphone-assisted lab-in-a-tube device using gold nanocluster-based aptasensor for detection of MUC1-overexpressed tumor cells.

Developing smartphone technology for point-of-care diagnosis is one of the current favorable trends in the field of biosensors. In fact, using smartphones can provide better accessibility and facility for rapid diagnosis of diseases. On the other hand, the detection of circulating tumor cells (CTCs) is one of the recent methods for the early diagnosis of cancer. Here, a new smartphone-assisted lab-in-a-tube device is introduced for the detection of Mucin 1 (MUC1) overexpressed tumor-derived cell lines using gold nanoclusters (GNCs)-based aptasensor. Accordingly, commercial polyurethane (PU) foam was first coated with graphene oxide (GO) to increase its surface area (8.45-fold), and improve its wettability. The surface of the resulting three-dimensional PU-GO (3DPU-GO) platform was then modified by MUC1 aptamer-GNCs to provide the required sensitivity and specificity through a turn "on/off" detection system. The proposed biosensor was first optimized with a spectrophotometer method. Afterward, findings were evaluated based on the red color intensity of the lab-in-a-tube system; and indicated the high ability of the biosensor for detection of MUC1-overexpressed tumor cell lines in the range of 250-20,000 cells mL-1 with a limit of detection of 221 cells mL-1. In addition, the developed biosensor showed a decent selectivity against positive-control cell lines (MCF-7, and HT-29) in comparison to negative-control cell lines (HEK293, and L929). Notably, the results represented good accordance with reference methods including spectroscopy devices. Ultimately, the results of this work bring a new perspective to the field of point-of-care detection and can be considered in future biosensors.

The dual role of Nrf2 in melanoma: a systematic review.

Melanoma is the most lethal type of skin cancer that originates from the malignant transformation of melanocytes. Although novel treatments have improved patient survival in melanoma, the overall prognosis remains poor. To improve current therapies and patients outcome, it is necessary to identify the influential elements in the development and progression of melanoma.Due to UV exposure and melanin synthesis, the melanocytic lineage seems to have a higher rate of ROS (reactive oxygen species) formation. Melanoma has been linked to an increased oxidative state, and all facets of melanoma pathophysiology rely on redox biology. Several redox-modulating pathways have arisen to resist oxidative stress. One of which, the Nrf2 (nuclear factor erythroid 2-related factor 2), has been recognized as a master regulator of cellular response to oxidative or electrophilic challenges. The activation of Nrf2 signaling causes a wide range of antioxidant and detoxification enzyme genes to be expressed. As a result, this transcription factor has lately received a lot of interest as a possible cancer treatment target.On the other hand, Nrf2 has been found to have a variety of activities in addition to its antioxidant abilities, constant Nrf2 activation in malignant cells may accelerate metastasis and chemoresistance. Hence, based on the cell type and context, Nrf2 has different roles in either preventing or promoting cancer. In this study, we aimed to systematically review all the studies discussing the function of Nrf2 in melanoma and the factors determining its alteration.

Leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.

Obesity may create a mitogenic microenvironment that influences tumor initiation and progression. The obesity-associated adipokine, leptin regulates energy metabolism and has been implicated in cancer development. It has been shown that some cell types other than adipocytes can express leptin and leptin receptors in tumor microenvironments. It has been shown that peroxisome proliferator-activated receptors (PPAR) agonists can affect leptin levels and vice versa leptin can affect PPARs. Activation of PPARs affects the expression of several genes involved in aspects of lipid metabolism. In addition, PPARs regulate cancer cell progression through their action on the tumor cell proliferation, metabolism, and cellular environment. Some studies have shown an association between obesity and several types of cancer, including breast cancer. There is some evidence that suggests that there is crosstalk between PPARs and leptin during the development of breast cancer. Through a systematic review of previous studies, we have reviewed the published relevant articles regarding leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.

The effects of morphine on vascular cell adhesion molecule 1(VCAM-1) concentration in lung cancer cells.

OBJECTIVE: Vascular cell adhesion molecule 1 (VCAM-1) plays an important role in tumour cell adhesion to endothelial cells. Some tumour cells also show aberrant expression of VCAM-1. Toll-like receptor 4 (TLR4) agonists can increase VCAM-1 expression. Morphine, an opioid receptor agonist, is also a TLR4 agonist. In this study, we aimed to evaluate whether morphine increase VCAM-1 expression in a TLR4 dependent manner. METHODS: A549 Lung cancer cells were treated with different doses of morphine and TLR4 antagonist for 24 and 48 h. TLR4 gene expression was evaluated by real-time PCR and VCAM-1 protein was measured by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Morphine enhanced mRNA expression of TLR4 and protein level of VCAM-1. TLR4 antagonist returned VCAM-1expression to the normal level. CONCLUSION: Morphine effects VCAM-1expressions via TLR4 in lung cancer cell line.