Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin. After treatment, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze PD-L1, CTLA-4, and VISTA gene expression in the SW-1116 cell line. The upregulation of VISTA expression showed a significant increase (p < 0.0001) in response to both chemotherapy agents. Moreover, the expression of CTLA-4 exhibited a remarkable level of significance (p < 0.0001), and PD-L1 expression also displayed notable significance (p < 0.0001). Chemotherapeutic agents heighten immune checkpoint gene expression, highlighting potential immune response pathway modulation.

Significance of PSCA as a novel prognostic marker and therapeutic target for cancer.

One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers.

Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

BACKGROUND: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. METHODS AND RESULTS: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). CONCLUSIONS: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.

Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options.

Small extracellular vesicles called exosomes play a crucial part in promoting intercellular communication. They act as intermediaries for the exchange of bioactive chemicals between cells, released into the extracellular milieu by a variety of cell types. Within the context of cancer progression, metastasis is a complex process that plays a significant role in the spread of malignant cells from their main site of origin to distant anatomical locations. This complex process plays a key role in the domain of cancer-related deaths. In summary, the trajectory of current research in the field of exosome-mediated metastasis is characterized by its unrelenting quest for more profound understanding of the molecular nuances, the development of innovative diagnostic tools and therapeutic approaches, and the unwavering dedication to transforming these discoveries into revolutionary clinical applications. This unrelenting pursuit represents a shared desire to improve the prognosis for individuals suffering from metastatic cancer and to nudge the treatment paradigm in the direction of more effective and customized interventions.

New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.

Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system's power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract.

Mapping current and future risk of scorpion sting from a species with low medical concern, Mesobuthus phillipsii (Scorpiones: Buthidae) in Iran.

Scorpion stings are one of the most important health challenges and high priority research topic in public health. In this study, we aimed to model habitat suitability of the Mesobuthus phillipsii (Pocock 1889), a species with low medical concern, under current and future climatic conditions in Iran. We also identified vulnerable populations to scorpion stings in the country. Scorpion sting risk modeling was done using an ensemble approach by considering two species distribution modeling methods: MaxEnt and Random Forest methods. Distribution modeling was performed using the sdm R package. The results showed that due to climate change in 2070, the high-risk areas will increase from 20,839 to 79,212 km2. Habitats with a moderate risk of scorpion stings will also increase from 139,347 to 222,833 km2. Consequently, the number of villages in high-risk areas of scorpion stings will increase from 2,870 to 7,017, while this number will increase from 12,759 to 20,104 in the case of medium-risk villages. The results of this study can be used for scorpion stings management in Iran. This study can be used as an example for similar studies on scorpions with high medical emergency.

Advances in siRNA delivery approaches in cancer therapy: challenges and opportunities.

Advancements in the clinical applications of small interfering RNA (siRNA) in cancer therapy have opened up new possibilities for precision medicine. siRNAs, as powerful genetic tools, have shown potential in targeting and suppressing the expression of specific genes associated with cancer progression. Their effectiveness has been further enhanced by incorporating them into nanoparticles, which protect siRNAs from degradation and enable targeted delivery. However, despite these promising developments, several challenges persist in the clinical translation of siRNA-based cancer therapy. This comprehensive review explores the progress and challenges associated with the clinical applications of siRNA in cancer therapy. This review highlights the use of siRNA-loaded nanoparticles as an effective delivery system for optimizing siRNA efficacy in various types of carcinomas and the potential of siRNA-based therapy as a genetic approach to overcome limitations associated with conventional chemotherapeutic agents, including severe drug toxicities and organ damage. Moreover, it emphasizes on the key challenges, including off-target effects, enzymatic degradation of siRNAs in serum, low tumor localization, stability issues, and rapid clearance from circulation that need to be addressed for successful clinical development of siRNA-based cancer therapy. Despite these challenges, the review identifies significant avenues for advancing siRNA technology from the laboratory to clinical settings. The ongoing progress in siRNA-loaded nanoparticles for cancer treatment demonstrates potential antitumor activities and safety profiles. By understanding the current state of siRNA-based therapy and addressing the existing challenges, we aim to pave the way for translating siRNA technology into effective oncologic clinics as an improved treatment options for cancer patients.

Cancer immunotherapy focusing on the role of interleukins: A comprehensive and updated study.

Cytokines bind to specific receptors on target cells to activate intracellular signaling pathways that control diverse cellular functions, such as proliferation, differentiation, migration, and death. They are essential for the growth, activation, and operation of immune cells and the control of immunological reactions to pathogens, cancer cells, and other dangers. Based on their structural and functional properties, cytokines can be roughly categorized into different families, such as the tumor necrosis factor (TNF) family, interleukins, interferons, and chemokines. Leukocytes produce interleukins, a class of cytokines that have essential functions in coordinating and communicating with immune cells. Cancer, inflammation, and autoimmunity are immune-related disorders brought on by dysregulation of cytokine production or signaling. Understanding cytokines' biology to create novel diagnostic, prognostic, and therapeutic methods for various immune-related illnesses is crucial. Different immune cells, including T cells, B cells, macrophages, and dendritic cells, and other cells in the body, including epithelial cells and fibroblasts, generate and secrete interleukins. The present study's main aim is to fully understand interleukins' roles in cancer development and identify new therapeutic targets and strategies for cancer treatment.

New immunotherapeutic approaches for cancer treatment.

Neoplasms are a worldwide recognized non-contagious disease which has the most mortality rate after cardiovascular diseases. For decades, there has been a vast amount of study on treatment methods of cancer which has led to conventional therapies such as chemotherapy, radiation therapy, surgery and so on. Clinicians and researchers believed that there is an urgent need, considering the high rate of incidence and prevalence, for an alternative treatment option which is more efficacious and has less adverse effects than the above-mentioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and became one of the fastest developing therapeutic approaches. Different kinds of immunotherapies are FDA approved and available for treatment of various cancer types. In this review, we have summarized the major immunotherapy methods including checkpoint inhibitors, CAR T cell therapies and cancer vaccines. Furthermore, application of combination therapy, precision medicine, biomarker discovery, overcoming resistance and reduction of adverse effects are discussed in this study.

Pattern-recognition receptors (PRRs) in SARS-CoV-2.

Pattern recognition receptors (PRRs) are specific sensors that directly recognize various molecules derived from viral or bacterial pathogens, senescent cells, damaged cells, and apoptotic cells. These sensors act as a bridge between nonspecific and specific immunity in humans. PRRs in human innate immunity were classified into six types: toll-like receptors (TLR), C-type lectin receptors (CLRs), nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and cyclic GMP-AMP (cGAMP) synthase (cGAS). Numerous types of PRRs are responsible for recognizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is immensely effective in prompting interferon responses. Detection of SARS-CoV-2 infection by PRRs causes the initiation of an intracellular signaling cascade and subsequently the activation of various transcription factors that stimulate the production of cytokines, chemokines, and other immune-related factors. Therefore, it seems that PRRs are a promising potential therapeutic approach for combating SARS-CoV-2 infection and other microbial infections. In this review, we have introduced the current knowledge of various PRRs and related signaling pathways in response to SARS-CoV-2.

Major depressive disorder: Biomarkers and biosensors.

Depressive disorders belong to highly heterogeneous psychiatric diseases. Loss of in interest in previously enjoyed activities and a depressed mood are the main characteristics of major depressive disorder (MDD). Moreover, due to significant heterogeneity in clinical presentation and lack of applicable biomarkers, diagnosis and treatment remains challenging. Identification of relevant biomarkers would allow for improved disease classification and more personalized treatment strategies. Herein, we review the current state of these biomarkers and then discuss diagnostic techniques of aimed to specifically target these analytes using state of the art biosensor technology.

An updated review of a novel method for examining P53 mutations in different forms of cancer.

In the past fifteen years, it has been clear that tumor-associated p53 mutations can cause behaviors distinct from those brought on by a simple loss of p53's tumor-suppressive function in its wild-type form. Many of these mutant p53 proteins develop oncogenic characteristics that allow them to encourage cell survival, invasion, and metastasis. But it is now understood that the immune response is also significantly influenced by the cancer cell's p53 status. The recruitment and activity of myeloid and T cells can be impacted by p53 loss or mutation in malignancies, allowing immune evasion and accelerating cancer growth. Additionally, p53 can work in immune cells, which can have various effects that either hinder or assist the growth of tumors. In this review article, we examined different mutations of P53 in some significant cancers, such as liver, colorectal, and prostate, and reviewed some new therapeutic approaches.

Dysregulation of P53 in breast cancer: Causative factors and treatment strategies.

One of the most prevalent cancers impacting women worldwide is breast cancer. Although there are several risk factors for breast cancer, the p53 gene's function has recently received much attention. The "gatekeeper" gene, or p53, is sometimes referred to as such since it is crucial in controlling cell proliferation and preventing the development of malignant cells. By identifying DNA damage and initiating cellular repair processes, p53 usually functions as a tumor-suppressor. But p53 gene alterations can result in a lack of function, allowing cells to divide out of control and perhaps triggering the onset of cancer. Various factors, such as mutation genes, signaling pathways, and hormones, can dysregulate P53 proteins and cause breast cancer. A promising strategy for individualized cancer treatment involves focusing on p53 mutations in breast cancer. While numerous techniques, including gene therapy and small compounds, have shown promise, further study is required to create safe and efficient treatments to target p53 mutations in breast cancer successfully.

Encouraging adoption of green manure technology to produce clean rice product.

Green manure is used as an environmentally friendly technology to produce clean agricultural products. This technology not only helps reduce environmental and health concerns, but can also increase productivity. Green manure is especially needed in the production of paddy. Because rice as a strategic product is the main food of people in many countries of the world. Rice production using green manure can enable countries to develop and increase healthy production. However, the acceptance of this technology is low in many rice producing countries. In this regard, this study used an integrated and extended version of the theory of planned behavior to predict and encourage the adoption of green manure technology in Iran. To collect the required data, a cross-sectional survey was performed among Iranian rice growers and the results of hypothesis testing were analyzed using partial least squares-based structural equation modeling. The results revealed that moral norms of green manure, attitude towards green manure, perceived behavioral control on using green manure, and trialability of green manure have positive and significant effects on intention towards using green manure. In addition, bootstrap analysis showed that moral norms of green manure and trialability of green manure positively and significantly mediated the (indirect) effects of subjective norms towards application of green manure on intention towards using green manure. The results led to important practical and theoretical implications that could provide new insights for policy-makers, planners, and practitioners to develop and encourage the adoption of green manure technology to produce clean and healthy agricultural products.

Consumer Attitude towards Genetically Modified Foods in Iran: Application of Three-Dimensional Model of Corporate Social Responsibility.

Although GM food production is considered an important strategy to meet the growing food needs of the population around the world, a majority of the GM food consumers express doubts about purchasing and eating them. However, it can be argued that consumers have different opinions about GM foods and their influence on human health and the natural environment. GM food producer Corporate Social Responsibility (CSR) may significantly affect such opinions, but the effect of this variable has been partially neglected in previous research studies. To address this gap, the present study investigates Iranian consumers' concerns about GM foods, trust in these products, and perception of GM food producer CSR as determinants of attitudes towards GM food. Data were collected from Iranian consumers. A cross-sectional survey research with a multi-stage random sampling approach was employed to capture the responses of 372 Iranian consumers. The results showed that consumers have both negative and positive attitudes towards GM foods. Perceived social equity, trust, and health concerns were the most important determinants of attitude towards GM foods. According to the results, these variables could account for 52.9% (Cox and Snell R2) and up to 70.6% (Nagelkerke R2) of the variance of the dependent variable. Furthermore, results revealed statistically significant differences among the consumers with different educational levels in terms of perceived social equity, perceived environmental responsibility, and environmental concern. The research contributes to the body of knowledge in GM food consumption by evolving the CSR to assess attitudes of users concerning GM foods.

Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.

OBJECTIVES: Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of RASSF1 and ATIC genes their potential implication in the pathogenesis of lung tumor in Iranian patients. METHODS: In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both RASSF1 and ATIC genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene's methylation. RESULTS: Methylation of RASSF1 gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of ATIC gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both RASSF1 and ATIC genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer. CONCLUSIONS: Methylation levels of both RASSF1 and ATIC genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.

How does Identity Theory contribute to the Continuance Use of E-learning: The mediating role of Inertia and moderating role of computer Self-efficacy.

Despite e-learning's rapid growth and significant benefits, especially during the COVID-19 pandemic, retaining students in this educational environment is a critical challenge in the post-corona era. Therefore, our research was conducted to explore how we can promote the continuance use of e-learning (CUEL) platforms. More specifically, this study examines how identity, inertia, and computer self-efficacy affect CUEL. Data were collected from 384 users and provided support for the model. The results indicated that social identity, relational identity, and inertia are critical determinants of CUEL. Furthermore, inertia mediates the relation between social identity and CUEL. In addition, we found that computer self-efficacy moderates the relation of inertia and relational identity with CUEL, but its moderating effect on the influence of social identity and CUEL is not supported. Finally, the theoretical and practical implications of this study are discussed.

The role of students' relational identity and autotelic experience for their innovative and continuous use of e-learning.

Over the last decades, using e-learning systems as an alternative format of education for traditional classroom has been growing in higher education and due to COVID-19 pandemic, this transition has been unprecedently accelerated. Although there is a large body of research on e-learning, little is known about the extent to which innovative and continuous use of e-learning systems can be influenced by students' social and motivational factors especially their relational identity and autotelic experience. This study collected data from 400 higher education students through a survey to explore the role of students' relational identity and autotelic experiences regarding their innovative and continuous use of e-learning systems while considering the mediating role of students' perception of relatedness. Collected data were analyzed using the structural equation modeling method. The results showed that students' relational identity and autotelic experience significantly influence the innovative and continuous use of e-learning. The results showed that relational identity and autotelic experience positivly associatewith innovative (ß = 0.190, t = 3.544; ß = 0.405, t = 7.973) and continuous use of e-learning (ß = 0.188, t = 3.115; ß = 0.344, t = 7.459) and relatedness plays a moderating role between relational identity and continuous use (ß = 0.194, t = 4.500, p = 0.000). Relatedness weakens the relationship between relational identity and innovative use of e-learning. However, it reinforces the relationship between relational identity and the continuous use of e-learning. It was found that relatedness strengthens the relationship between autotelic experience with innovative and continuous use of e-learning. The results of this study provide evidence of how students' social and motivational factors can influence their approaches to the innovative and continuous use of e-learning systems. We discuss these results and provide agenda for future practical and professional work.

Brain CT Scan, Sonography and EEG Findings in Neonates with Seizure.

Objectives: This study aimed to determine the frequency of different types, causes, and abnormal findings of brain computed tomography scan (CT scan) and ultrasonography (US) and multichannel- electroencephalography (EEG) in neonates with seizure. The ability of brain CT scan was also compared with US in terms of detecting the underlying causes of neonatal seizures. Materials & Methods: In this cross-sectional retrospective study, the medical records of 90 neonates younger than 28 days with the definite diagnosis of seizure were reviewed. The data were analyzed using SPSS 22 through descriptive and Exact fisher tests. Results: Totally, 90 newborns (M: F = 1.5:1) with mean age of 63.11 ± 32.8 days were enrolled. 35.5% of newborns were born before the 37th week of pregnancy. In this study, 45.6% of EEG findings, 22% of brain CT scan findings, and 12.5% of US findings were abnormal. The automatisms (38.9%) and benign idiopathic neonatal seizure (70.7%) were the most common seizure type and cause respectively. The hypoxic Ischemic encephalopathy was the most common abnormal finding (30%) in brain CT scan. Conclusions: Given the accuracy of EEG in detection of brain pathologies, where available, all neonatal seizures should be initially confirmed using EEG. Radiologic investigations (CT scan, US) off the head/ cranium should be done to detect the cause of neonatal seizure. The capacity of brain CT scan to detect underlying causes of neonatal seizures is more than US.