Synergistic anticancer effects of co-delivery of linc-RoR siRNA and curcumin using polyamidoamine dendrimers against breast cancer.

Breast cancer resistance to chemotherapy necessitates novel combination therapeutic approaches. Linc-RoR is a long intergenic noncoding RNA that regulates stem cell differentiation and promotes metastasis and invasion in breast cancer. Herein, we report a dual delivery system employing polyamidoamine dendrimers to co-administer the natural compound curcumin and linc-RoR siRNA for breast cancer treatment. Polyamidoamine dendrimers efficiently encapsulated curcumin and formed complexes with linc-RoR siRNA at an optimal N/P ratio. In MCF-7 breast cancer cells, the dendriplexes were effectively internalized and the combination treatment synergistically enhanced cytotoxicity, arresting the cell cycle at the G1 phase and inducing apoptosis. Linc-RoR gene expression was also significantly downregulated. Individual treatments showed lower efficacy, indicating synergism between components. Mechanistic studies are warranted to define the molecular underpinnings of this synergistic interaction. Our findings suggest dual delivery of linc-RoR siRNA and curcumin via dendrimers merits further exploration as a personalized therapeutic approach for overcoming breast cancer resistance.

Liposomal delivery system/adjuvant for tuberculosis vaccine.

As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next-generation TB vaccines.

Designing a humanized immunotoxin based on DELTA-stichotoxin-Hmg2a toxin: an in silico study.

Breast cancer remains the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women. HER2 positive subtype includes 15-20% of breast cancer cases. This receptor could be an appropriate mark for targeting breast cancer cells. Immunotherapy methods compared to current cancer treatment methods have the lowest side effects. DELTA-stichotoxin-Hmg2a is isolated from the sea anemone and kills cells through pore formation. In the current study, we designed and evaluated an immunotoxin composed of pertuzumab and DELTA-stichotoxin-Hmg2a-derived scFv by bioinformatics tools. The designed immunotoxin was constructed using the amino acid sequences. Then, secondary structure and physico-chemical features were studied, and the tertiary structure of the immunotoxin was built according to the homology modeling methods. The validation and allergenicity of the model were assessed. The immunotoxin and receptor were docked and molecular dynamics simulation indicated the construct stability. The analysis results indicated that the construct is a stable protein that could have a natural-like structure and would not be an allergen, so this immunotoxin could effectively target HER2 receptors. Therefore, our designed immunotoxin could be an appropriate immunotoxin against HER2-positive breast cancer and could be a challenging topic for future in vitro and in vivo studies.

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.

microRNA in inflammatory bowel disease at a glance.

Inflammatory bowel disease (IBD) as a chronic inflammation in colon and small intestine has two subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Genome studies have shown that UC and CD are related to microRNAs (miRNAs) expression in addition to environmental factors. This article reviews important researches that have recently been done on miRNAs roles in CD and UC disease. First, miRNA is introduced and its biogenesis and function are discussed. Afterward, roles of miRNAs in inflammatory processes involved in IBD are showed. Finally, this review proposes some circulating and tissue-specific miRNAs, which are useful for CD and UC fast diagnosis and grade prediction. As a conclusion, miRNAs are efficient diagnostic molecules especially in IBD subtypes discrimination and can be used by microarray and real time PCR methods for disease detection and classification.