Chondroitin sulfate-tocopherol succinate modified exosomes for targeted drug delivery to CD44-positive cancer cells.

Exosomes (Exos), natural nanovesicles released by various cell types, show potential as an effective drug delivery platform due to their intrinsic role as transporters of biomolecules between different cells. However, Exos functionalization with targeting ligands is a critical step to enhance their targeting capability, which could be challenging. In this study, Exos were modified to specifically bind to CD44-positive cells by anchoring chondroitin sulfate (CS) to their surface. Exo modification was facilitated with CS conjugation with alpha-tocopherol succinate (TOS) as an anchorage. The modified Exos were utilized for delivering curcumin (Cur) to pancreatic cancer (PC) cells. In vitro Cur release studies revealed that Exos play a crucial role in maintaining Cur within themselves, demonstrating their potential as effective carriers for drug delivery to targeted locations. Notably, Cur loaded into the modified Exos exhibited enhanced cytotoxicity compared to unmodified Exo-Cur. Meanwhile, Exo-Cur-TOS-CS induced apoptosis more effectively in AsPC-1 cells than unmodified Exos (70.2 % versus 56.9 %). It is worth mentioning that with CD44-mediated cancer-specific targeting, Exo-CS enabled increased intracellular accumulation in AsPC-1 cells, showing promise as a targeted platform for cancer therapy. These results confirm that Exo modification has a positive impact on enhancing the therapeutic efficacy and cytotoxicity of drugs.

The Oxidative Status and Na+/K+-ATPase Activity in Obsessive-Compulsive Disorder: A Case Control Study.

Background: Oxidative stress is involved in pathogenesis of some psychiatric disorders. To examine the role of oxidative stress in the etiopathogenesis of obsessive-compulsive disorder (OCD), we aimed to determine oxidative stress indices, including malondialdehyde (MDA) levels in serum and red blood cells (RBC) membrane, total antioxidant capacity (TAC), serum glutathione (GSH) levels, serum antioxidant vitamins (A and E), and Na+/K+-ATPase activity, in patients with the mentioned disorder vs. healthy controls. Method: 39 OCD patients diagnosed based on Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and 39 volunteer healthy subjects were included in this study. MDA levels in serum and RBC membrane were measured using fluorometric method. Serum TAC level, serum GSH level, and Na+/K+-ATPase activity were also measured using spectrophotometric methods. Serum levels of vitamins were calculated by reversed-phase high-performance liquid chromatography (RP-HPLC). Result: There was a significantly higher MDA level in serum (p < 0.0001) and RBC membrane (p = 0.002) of OCD patients compared with those in controls. A significant reduction in vitamin A (p = 0.001) and vitamin E (p = 0.024) levels was found in OCD patients vs. controls. There was significantly lower activity of erythrocyte membrane Na+/K+-ATPase in RBC membrane of OCD patients vs. controls (p < 0.0001). Conclusion: Our findings indicate significantly higher levels MDA in both serum and RBC membrane, lower levels of serum vitamins A and E, and lower activity of membrane Na+/K+-ATPase in OCD patients compared to controls. These suggest an imbalance between oxidant and antioxidant factors in OCD patients that might play a fundamental role in the etiopathogenesis of OCD.

Epigenetic modifications and obsessive-compulsive disorder: what do we know?

Obsessive-Compulsive Disorder (OCD) is a chronic, severe disabling neuropsychiatric disorder whose pathophysiology is not yet well defined. Generally, the symptom onset occurs during pre-adult life and affects subjects in different life aspects, including professional and social relationships. Although robust evidence indicates the presence of genetic factors in the etiopathology of OCD, the entirely mechanisms are not totally clarified. Thus, the possible interactions between genes and environmental risk factors mediated by epigenetic mechanisms should be sought. Therefore, we provide a review of genetic and epigenetic mechanisms related to OCD with a deep focus on the regulation of critical genes of the central nervous system seeking possible potential biomarkers.

Modification of Extracellular Vesicle Surfaces: An Approach for Targeted Drug Delivery.

Extracellular vesicles (EVs) are a promising drug delivery vehicle candidate because of their natural origin and intrinsic function of transporting various molecules between different cells. Several advantages of the EV delivery platform include enhanced permeability and retention effect, efficient interaction with recipient cells, the ability to traverse biological barriers, high biocompatibility, high biodegradability, and low immunogenicity. Furthermore, EV membranes share approximately similar structures and contents to the cell membrane, which allows surface modification of EVs, an approach to enable specific targeting. Enhanced drug accumulation in intended sites and reduced adverse effects of chemotherapeutic drugs are the most prominent effects of targeted drug delivery. In order to improve the targeting ability of EVs, chemical modification and genetic engineering are the most adopted methods to date. Diverse chemical methods are employed to decorate EV surfaces with various ligands such as aptamers, carbohydrates, peptides, vitamins, and antibodies. In this review, we introduce the biogenesis, content, and cellular pathway of natural EVs and further discuss the genetic modification of EVs, and its challenges. Furthermore, we provide a comprehensive deliberation on the various chemical modification methods for improved drug delivery, which are directly related to increasing the therapeutic index.

Administration of stem cells against cardiovascular diseases with a focus on molecular mechanisms: Current knowledge and prospects.

Cardiovascular diseases (CVDs) are a serious global concern for public and human health. Despite the emergence of significant therapeutic advances, it is still the leading cause of death and disability worldwide. As a result, extensive efforts are underway to develop practical therapeutic approaches. Stem cell-based therapies could be considered a promising strategy for the treatment of CVDs. The efficacy of stem cell-based therapeutic approaches is demonstrated through recent laboratory and clinical studies due to their inherent regenerative properties, proliferative nature, and their capacity to differentiate into different cells such as cardiomyocytes. These properties could improve cardiovascular functioning leading to heart regeneration. The two most common types of stem cells with the potential to cure heart diseases are induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). Several studies have demonstrated the use, efficacy, and safety of MSC and iPSCs-based therapies for the treatment of CVDs. In this study, we explain the application of stem cells, especially iPSCs and MSCs, in the treatment of CVDs with a focus on cellular and molecular mechanisms and then discuss the advantages, disadvantages, and perspectives of using this technology in the treatment of these diseases.

An overview on role of nutrition on COVID-19 immunity: Accumulative review from available studies.

The novel coronavirus infection (COVID-19) conveys a serious global threat to health and economy. A common predisposing factor for development to serious progressive disease is presence of a low-grade inflammation, e.g., as seen in diabetes, metabolic syndrome, and heart failure. Micronutrient deficiencies may also contribute to the development of this state. Therefore, the aim of the present study is to explore the role of the nutrition to relieve progression of COVID-19. According PRISMA protocol, we conducted an online databases search including Scopus, PubMed, Google Scholar and web of science for published literatures in the era of COVID-19 Outbreak regarding to the status of nutrition and COVID-19 until December 2021. There were available studies (80 studies) providing direct evidence regarding the associations between the status of nutrition and COVID-19 infection. Adequate nutritional supply is essential for resistance against other viral infections and also for improvement of immune function and reduction of inflammation. Hence, it is suggested that nutritional intervention which secures an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate its course. We also recommend initiation of adequate nutritional supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority for applying this nutritive adjuvant therapy that should be started prior to administration of specific and supportive medical measures.

Correlations between single nucleotide polymorphisms in obsessive-compulsive disorder with the clinical features or response to therapy.

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder, in which the patient endures intrusive thoughts or is compelled to perform repetitive or ritualized actions. Many cases of OCD are considered to be familial or heritable in nature. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of OCD. Among the internal factors, genetic modifications play a critical role in the pathophysiological process. Despite many investigations performed to determine the candidate genes, the precise genetic factors involved in the disease remain largely undetermined. The present review summarizes the single nucleotide polymorphisms that have been proposed to be associated with OCD symptoms, early onset disease, neuroimaging results, and response to therapy. This information could help us to draw connections between genetics and OCD symptoms, better characterize OCD in individual patients, understand OCD prognosis, and design more targeted personalized treatment approaches.

Psychological assessment in infertility: A systematic review and meta-analysis.

Infertility is a prevalent worldwide health issue and is defined by the World Health Organization (WHO) as a global health problem. Considering the importance of the psychological dimensions of infertility, various measurement tools have been used to measure the variables involved in infertility, of which the most widely used are the following: the Symptom Checklist 90 (SCL90), the Brief Symptom Inventory (BSI), the State-Trait Anxiety Inventory Form (STAI), and the Depression Anxiety Stress Scale (DASS). Therefore, given the problems of infertile people in terms of psychological dimensions, the aim of this meta-analysis was to assess the psychological assessment score in infertility. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, we applied an online database with no time restriction. Data were gathered using a random-effect model to estimate the standard mean difference (SMD) for the evaluation of the strength of association analyses. Our data demonstrated a significant higher SCL90 score (CI SCL90: 0.96, 0.34-1.57, heterogeneity: 94%, p heterogeneity < 0.001), and a non-significant higher DASS score (CI Anxiety : 0.82, -0.14 to 1.79; CI Depression : 0.8, -0.28 to 1.87; and CI Stress : 0.82, -0.24 to 1.88). It is essential to seek for strategies to help infertile patients overcome their infertility-related psychological problems.

MicroRNAs and Synaptic Plasticity: From Their Molecular Roles to Response to Therapy.

Synaptic plasticity is the ability of synapses to weaken or strengthen over time, in response to changes in the activity of the neurons. It is orchestrated by a variety of genes, proteins, and external and internal factors, especially epigenetic factors. MicroRNAs (miRNAs) are well-acknowledged epigenetic modulators that regulate the translation and degradation of target genes in the nervous system. Increasing evidence has suggested that a number of miRNAs play important roles in modulating various aspects of synaptic plasticity. The deregulation of miRNAs could be associated with pathological alterations in synaptic plasticity, which could lead to different CNS-related diseases. Herein, we provide an update on the role of miRNAs in governing synaptic plasticity. In addition, we also summarize recent researches on the role of miRNAs in drug addiction, and their targets and mechanism of action. Understanding of the way in which miRNAs contribute to synaptic plasticity provides rational clues in establishing the novel biomarkers and new therapeutic strategies for the diagnosis and treatment of plasticity-related diseases and drug addiction.

Roles of Non-coding RNAs and Angiogenesis in Glioblastoma.

One of the significant hallmarks of cancer is angiogenesis. It has a crucial function in tumor development and metastasis. Thus, angiogenesis has become one of the most exciting targets for drug development in cancer treatment. Here we discuss the regulatory effects on angiogenesis in glioblastoma (GBM) of non-coding RNAs (ncRNAs), including long ncRNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). These ncRNAs may function in trans or cis forms and modify gene transcription by various mechanisms, including epigenetics. NcRNAs may also serve as crucial regulators of angiogenesis-inducing molecules. These molecules include, metalloproteinases, cytokines, several growth factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor, hypoxia-inducible factor-1, and epidermal growth factor), phosphoinositide 3-kinase, mitogen-activated protein kinase, and transforming growth factor signaling pathways.

Joint application of biochemical markers and imaging techniques in the accurate and early detection of glioblastoma.

Glioblastoma is a primary brain tumor with the most metastatic effect in adults. Despite the wide range of multidimensional treatments, tumor heterogeneity is one of the main causes of tumor spread and gives great complexity to diagnostic and therapeutic methods. Therefore, featuring noble noninvasive prognostic methods that are focused on glioblastoma heterogeneity is perceived as an urgent need. Imaging neuro-oncological biomarkers including MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation status, tumor grade along with other tumor characteristics and demographic features (e.g., age) are commonly referred to during diagnostic, therapeutic and prognostic processes. Therefore, the use of new noninvasive prognostic methods focused on glioblastoma heterogeneity is considered an urgent need. Some neuronal biomarkers, including the promoter methylation status of the promoter MGMT, the characteristics and grade of the tumor, along with the patient's demographics (such as age and sex) are involved in diagnosis, treatment, and prognosis. Among the wide array of imaging techniques, magnetic resonance imaging combined with the more physiologically detailed technique of H-magnetic resonance spectroscopy can be useful in diagnosing neurological cancer patients. In addition, intracranial tumor qualitative analysis and sometimes tumor biopsies help in accurate diagnosis. This review summarizes the evidence for biochemical biomarkers being a reliable biomarker in the early detection and disease management in GBM. Moreover, we highlight the correlation between Imaging techniques and biochemical biomarkers and ask whether they can be combined.

Malondialdehyde concentrations in obsessive-compulsive disorder: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate serum and plasma malondialdehyde (MDA) levels in patients with obsessive-compulsive disorder (OCD) in comparison to healthy controls. METHODS: Following the PRISMA protocol, we searched for the relevant studies through the databases of Scopus, PubMed, Google Scholar, and web of science until September 2019 with no time restriction. Overall, nine studies were included in the current meta-analysis. Data were pooled using a random-effects model; in addition, standard mean difference (SMD) and/or weight mean difference (WMD) was calculated. Cochran's Q test and I-square (I2) statistics were used to evaluate between-study heterogeneity. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of the included studies. Statistical analyses were done using the STATA version 14. RESULTS: Our systematic review included nine case-control studies (including 367 cases and 337 controls). Pooling findings from these studies showed a significantly higher MDA level in OCD patient compared to control groups (SMD = 1.62; 95% CI [0.53, 2.72]; I2 = 96.9%; Pheterogeneity (Ph) < 0.001). This finding remained unchanged among studies which reported MDA in the same unit (WMD = 1.93; 95% CI [0.27, 3.59]; I2 = 99.2%; Ph < 0.001). Subgroup analysis by the study location and sample size revealed findings that were also significant. CONCLUSION: We found that MDA levels are higher in OCD patients than healthy controls. This finding highlights the importance of inflammatory responses in OCD patients that should be considered for future investigations. Further studies are recommended to expand current knowledge on this issue.

Serum Vitamins and Homocysteine Levels in Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

Vitamin and homocysteine (Hcy) alternations have been associated with psychiatric disorders. The aim of this meta-analysis was to assess the association of serum vitamin and Hcy levels with obsessive-compulsive disorder (OCD). Following PRISMA protocol, we used the databases including Scopus, PubMed, Google Scholar, and Web of Science with no time restriction. Data were pooled using a random-effects model and/or fixed-effects model to estimate the standard mean difference (SMD) for evaluation of the strength of association analyses. Our data showed a significant reduction in vitamin B12 (SMD = -0.58, 95% CI = -1.08 to -0.08, p = 0.02, I2 = 65%; pheterogeneity = 0.06), vitamin E (SMD = -0.89, 95% CI = -1.23 to -0.56, p < 0.00001, I2 = 23%; pheterogeneity = 0.26), and vitamin C (SMD = -1.40, 95% CI = -2.44 to -0.36, p = 0.008, I2 = 92%; pheterogeneity < 0.0001) in OCD patients. In addition, the findings showed significantly higher levels of Hcy (SMD = 1.11, 95% CI = [0.48, 1.75], p = 0.0006, I2 = 73%; ph = 0.02) in patients compared to controls. Also, our data showed that vitamin B9 and D levels are not associated with OCD (vitamin B9: SMD = -0.23, 95% CI = -1.01 to 0.55, p = 0.56, I2 = 88%; pheterogeneity < 0.0001; vitamin D: SMD = -0.63, 95% CI = -1.41 to 0.15, p = 0.11, I2 = 88%; pheterogeneity = 0.0002). Our findings support significant impacts of Hcy and vitamin B12, E, and C levels in OCD pathogenesis. This will be important for prevention and treatment of OCD. However, further studies are recommended to elucidate more accurate conclusions.