Elimination of Human Papillomavirus and Cervical Pathological Microbiota with Photodynamic Therapy in Women from Mexico City with Cervical Intraepithelial Neoplasia I.

Cervical carcinoma (CC) is the second cause of cancer death in Mexican women. It starts with premalignant lesions known as Intraepithelial Cervical Neoplasia (CIN) that can develop due to infection by Human Papillomavirus (HPV) and other microorganisms. Current CIN therapy involves invasive methods that affect cervix integrity and fertility; we propose the use of photodynamic therapy (PDT) as a strategy with few side effects. In this work, the effectiveness of PDT for CIN I, HPV and pathogenic vaginal microbiota elimination in 29 women of Mexico City with CIN I, CIN I + HPV and HPV diagnosis was determined. After 6 months of PDT application, HPV infection was eliminated in 100% of the patients (P < 0.01), CIN I + HPV in 64.3% (P < 0.01) and CIN I in 57.2% (P > 0.05). PDT also eliminated pathogenic microorganisms: Chlamydia trachomatis in 81% of the women (P < 0.001) and Candida albicans in 80% (P < 0.05), without affecting normal microbiota since Lactobacillus iners was eliminated only in 5.8% of patients and the opportunistic Gardnerella vaginalis in 20%. These results show that PDT was highly effective in eradicating HPV and pathogenic microorganisms, suggesting that PDT is a promising therapy for cervical infections.

Attachment and In Vitro Transfection Efficiency of an Anti-Rabies Chitosan-DNA Nanoparticle Vaccine.

In Mexico, urban rabies has been reduced during the last decade thanks to intensive canine control and vaccination campaigns; however, rabies transmitted by wild animals, especially by bats, has been increasing due to vampire bats feeding on livestock. Vampire bat populations has been controlled by culling with vampiricides, reducing indiscriminately other bat species. Hence, bat vaccination for rabies offers an alternative for culling. Nevertheless, available rabies vaccines are not suitable for their use in wildlife from emerging countries. This project presents an alternative for the use of plasmid vaccines using bio-nanotechnology, to create low-cost and accessible vaccines. To accomplish this goal, chitosan nanoparticles were synthesized by ionic gelation and conjugated by coacervation with a pDNA rabies vaccine to test their attachment efficiency. Also, the conjugate was functionalized with Protoporphyrin IX and Folic acid as biomarkers. The nanoparticles complex was characterized by ultraviolet visible spectroscopy, infrared spectroscopy, transmission electron microscopy, dynamic light scattering, and the Z potential was obtained. In vitro tests were performed on cell viability and transfection. The nanoparticles possessed a low polydispersity, a mean size of 118.5 ± 13.6 nm and a Z potential of 17.3 mV. The attachment efficiency was of 100% independent of pDNA added. In contrast to functionalized nanoparticles which showed a max attachment efficiency of 99.6% dependent of pDNA concentration and the method of functionalization. The conjugate did not influence the viability and they improved the transfection efficiency. Results suggest that these nanoparticles are easy to prepare, inexpensive, and exhibit potential for plasmid delivery as it improves transfection efficiency of pDNA vaccines.

CRISPR-dCas9-Based Artificial Transcription Factors to Improve Efficacy of Cancer Treatment With Drug Repurposing: Proposal for Future Research.

Due to the high resistance that cancer has shown to conventional therapies, it is difficult to treat this disease, particularly in advanced stages. In recent decades, treatments have been improved, being more specific according to the characteristics of the tumor, becoming more effective, less toxic, and invasive. Cancer can be treated by the combination of surgery, radiation therapy, and/or drug administration, but therapies based on anticancer drugs are the main cancer treatment. Cancer drug development requires long-time preclinical and clinical studies and is not cost-effective. Drug repurposing is an alternative for cancer therapies development since it is faster, safer, easier, cheaper, and repurposed drugs do not have serious side effects. However, cancer is a complex, heterogeneous, and highly dynamic disease with multiple evolving molecular constituents. This tumor heterogeneity causes several resistance mechanisms in cancer therapies, mainly the target mutation. The CRISPR-dCas9-based artificial transcription factors (ATFs) could be used in cancer therapy due to their possibility to manipulate DNA to modify target genes, activate tumor suppressor genes, silence oncogenes, and tumor resistance mechanisms for targeted therapy. In addition, drug repurposing combined with the use of CRISPR-dCas9-based ATFs could be an alternative cancer treatment to reduce cancer mortality. The aim of this review is to describe the potential of the repurposed drugs combined with CRISPR-dCas9-based ATFs to improve the efficacy of cancer treatment, discussing the possible advantages and disadvantages.