Investigating the inhibitory effects of Seidlitzia rosmarinus extract on the amyloid fibril formation of ҡ-casein in the presence of dextran

Background: Formation of amyloid fibrils has been associated with different protein aggregation diseases. Many studies indicate that many proteins can be converted in vitro into amyloid structures. Isolated ҡ-casein (ҡ-CN) spontaneously forms amyloid fibrils under physiological conditions, so it is a convenient model for researching generic aspect of fibril formation.Materials and Methods: In this study the effect of aqueous extract of S. rosmarinus on the amyloid formation of ҡ-CN in the presence and absence of crowding agent, dextran, have been examined using Thioflavin T binding (ThT) assay, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy.Results: ThT binding assay showed that dextran increased the rate of amyloid fibril formation and S. rosmarinus extract retarded the amyloid fibril formation in κ-CN. In the presence of dextran however, the effect of   S. rosmarinus extract on the amyloid formation of ҡ-CN was less than in its absence.Fluorescence spectroscopy results also demonstrated that dextran led to unfolding and increased the exposure hydrophobic area in ҡ-CN. S. rosmarinus extract efficiency decreased the exposure of hydrophobic regions in κ-CN, whereas in the presence of dextran this effect of extract was reduced.CD spectroscopy results exhibited that incubation of κ-CN with S. rosmarinus extract prevented a structural transition to a β-sheet. CD spectroscopy results also indicated that by adding dextran to reduced κ-CN β-sheet structures observed, which indicates structural change. S. rosmarinus extract however, prevented transition to β-sheet structural.Conclusion: In conclusion our finding suggests that S. rosmarinus extract prevents amyloid fibril formation in κ-CN, although this effect decreased in the presence of dextran

Hepatotoxicity Among Poisoned Patients: A Cross-sectional Study

Background: Drug-induced liver injury is a major cause of hepatitis worldwide. In patients diagnosed with acute poisoning, drug-induced liver injury is a critical challenge. This study aims to evaluate the pattern of hepatotoxicity in poisoned patients admitted to Loghman Hakim Hospital.Methods: In this cross-sectional study that was conducted at Loghman Hakim hospital, the clinical records of poisoned patients were evaluated and patients with hepatotoxicity were selected for final analysis. The clinical and para-clinical information of these patients was recorded. The SPSS software, version 23. was used for statistical analysis.Results: A total of 260 cases were included in this study. The Mean±SD age of patients was 38.24±16.29 years and most of them were male (79.2%). Patients with narcotics poisoning had the highest prevalence (38.5%), especially when they were taken together with acetaminophen or benzodiazepine. In addition, among the patients studied, those with underlying cardiovascular disease are more likely to develop hepatotoxicity.Conclusion: In conclusion, among people with various types of poisoning, it seems that narcotics (opium, heroin, methadone, etc.), particularly when taken together with acetaminophen or benzodiazepines, cause hepatotoxicity and increase serum levels of liver aminotransferases. Also, in the study population, patients with underlying cardiovascular disease had a higher chance of liver injury. Therefore, clinicians are recommended to accurately monitor the sign and symptoms of hepatotoxicity in these populations

DOT: A flexible multi-objective optimization framework for transferring features across single-cell and spatial omics

Single-cell RNA sequencing (scRNA-seq) and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. On one hand, scRNA-seq provides information about a large portion of the transcriptome for individual cells, but lacks the spatial context. On the other hand, spatially-resolved measurements come with a trade-off between resolution and gene coverage. Combining scRNA-seq with different spatially-resolved technologies can thus provide a more complete map of tissues with enhanced cellular resolution and gene coverage. Here, we propose DOT, a novel multi-objective optimization framework for transferring cellular features across these data modalities. DOT is flexible and can be used to infer categorical (cell type or cell state) or continuous features (gene expression) in different types of spatial omics. Our optimization model combines practical aspects related to tissue composition, technical effects, and integration of prior knowledge, thereby providing flexibility to combine scRNA-seq and both low- and high-resolution spatial data. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data across different tissues. DOT is freely available and can be deployed efficiently without large computational resources; typical cases-studies can be run on a laptop, facilitating its use.Comment: 36 pages, 6 figure

Homing and mobilization of hematopoietic stem cells

Hematopoietic stem and progenitor cells (HSPCs) are non-stop travelers throughout body in both time and space. Understanding the mechanism of HSPCs homing and mobilization is important to enhance the efficacy at bone marrow transplantation and cellular therapy. Mobilized HSPCs has largely replaced than the use of bone marrow as a source of stem cells for both allogeneic and autologous stem cell transplantation. This review describes the specific factors which play a key role in homing and mobilization of HSPCs, includes SDF-1 and its receptor CXCR4, proteases (MMPs and CPM). Moreover, chemokines inducing rapid HPSCs mobilization would be discussed. In this article we showed that many factors such as adhesion molecules and SDF-1/CXCR4 have critical roles in homing hematopoietic stem cells and G.CSF, MMPs, adhesion molecules and ROS involvement in mobilization of stem cells. According to above, we can be rich the peripheral blood of HSPCS using of this factors and antagonist for this receptors on the osteoblastic cells or/and HSPCs to bone marrow transplant

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.Sección Deptal. de Bioquímica y Biología Molecular (Biológicas)Fac. de Ciencias BiológicasTRUEEuropean UnionNextGeneration (EU/PRTR)Ministerio de Ciencia e Innovación (MICINN)/Agencia Estatal de Investigación (AEI)Ministerio de UniversidadesUniversidad Complutense de Madrid (UCM)pu

DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics

Abstract Single-cell transcriptomics and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. However, they suffer from lack of spatial information and a trade-off of resolution and gene coverage, respectively. We propose DOT, a multi-objective optimization framework for transferring cellular features across these data modalities, thus integrating their complementary information. DOT uses genes beyond those common to the data modalities, exploits the local spatial context, transfers spatial features beyond cell-type information, and infers absolute/relative abundance of cell populations at tissue locations. Thus, DOT bridges single-cell transcriptomics data with both high- and low-resolution spatially-resolved data. Moreover, DOT combines practical aspects related to cell composition, heterogeneity, technical effects, and integration of prior knowledge. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data