The application of plant-exosome-like nanovesicles as improved drug delivery systems for cancer vaccines.

The use of cancer immunotherapeutics is currently increasing. Cancer vaccines, as a form of immunotherapy, are gaining much attention in the medical community since specific tumor-antigens can activate immune cells to induce an anti-tumor immune response. However, the delivery of cancer vaccines presents many issues for research scientists when designing cancer treatments and requires further investigation. Nanoparticles, synthetic liposomes, bacterial vectors, viral particles, and mammalian exosomes have delivered cancer vaccines. In contrast, the use of many of these nanotechnologies produces many issues of cytotoxicity, immunogenicity, and rapid clearance by the mononuclear phagocyte system (MPS). Plant-exosome-like nanovesicles (PELNVs) can provide solutions for many of these challenges because they are innocuous and nonimmunogenic when delivering nanomedicines. Hence, this review will describe the potential use of PELNVs to deliver cancer vaccines. In this review, different approaches of cancer vaccine delivery will be detailed, the mechanism of oral vaccination for delivering cancer vaccines will be described, and the review will discuss the use of PELNVs as improved drug delivery systems for cancer vaccines via oral administration while also addressing the subsequent challenges for advancing their usage into the clinical setting.

The use of plant-derived exosome-like nanoparticles as a delivery system of CRISPR/Cas9-based therapeutics for editing long non-coding RNAs in cancer colon cells.

Colon cancer is one of the leading causes of cancer in the United States. Colon cancer develops from the many gene mutations found in the genomes of colon cancer cells. Long non-coding RNAs (lncRNAs) can cause the development and progression of many cancers, including colon cancer. LncRNAs have been and could be corrected through the gene-editing technology of the clustered repeats of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system to reduce the proliferation of cancer cells in the colon. However, many current delivery systems for transporting CRISPR/Cas9-based therapeutics in vivo need more safety and efficiency. CRISPR/Cas9-based therapeutics require a safe and effective delivery system to more directly and specifically target cancer cells present in the colon. This review will present pertinent evidence for the increased efficiency and safety of using plant-derived exosome-like nanoparticles as nanocarriers for delivering CRISPR/Cas9-based therapeutics to target colon cancer cells directly.

Plasmid carriage and the natural complexity of bacterial populations contributes to plasmid persistence / El transporte de plásmidos y la complejidad natural de las poblaciones bacterianas contribuyen a la persistencia del plásmido

Introduction: Plasmids carry and transport genes that assist their hosts to survive in many environments. Many studies have examined the conditions for plasmid persistence in bacterial populations. A limitation includes that a majority of the mathematical models for examining plasmid persistence only included bacteria from similar colonies. However, most bacterial cells inhabit complex communities where plasmids disseminate between varied bacterial host cells. Thus, there is a gap in knowledge concerning the persistence of plasmids in natural bacterial populations. To address a few of these gaps in knowledge, the present study attempted to examine the effects of plasmid carriage on intrinsic stages of bacterial populations in Bacillus subtilis co-cultures. Material and methods: B. subtilis cells were transformed with CRISPR-hCas-9 plasmid vectors where the natural phases of bacterial growth, biofilm production, and antibiotic resistance were examined in relation to plasmid carriage. These three natural phases were measured in relation to plasmid carriage through in vitro co-culture assays. Results: After calculating the CFU/mL, bacterial growth in the B. subtilis-Carrier with Escherichia coli (B. sub-C-E. coli) and Vibrio harveyi (B. sub-C-VH) co-cultures significantly decreased with a paired-t-test two-tailed P=0. The WT B. subtilis-V.H samples, the B. subtilis Carrier-V.H co-cultures, and the controls each scored a total of 40, 47, and 46 of crystal violet (CV) intensity of biofilm, respectively. Biofilm formation decreased after co-culturing E. coli with the B. subtilis-Carrier, yielding a P<0.001. The antibiotic resistance levels of the co-cultures increased by 3% for the B. sub-C-V.H samples while the B. sub-C-E. coli co-cultures decreased in antibiotic sensitivity by approximately 1.5%. Conclusions: Plasmid carriage contributes to plasmid persistence via altering the natural phases of bacterial populations (AU)

Introducción: Los plásmidos portan y transportan genes que ayudan a sus huéspedes a sobrevivir en muchos entornos. Muchos estudios han examinado las condiciones para la persistencia de plásmidos en poblaciones bacterianas. Una limitación incluye que la mayoría de los modelos matemáticos para examinar la persistencia de plásmidos solo incluyeron bacterias de colonias similares. Sin embargo, la mayoría de las células bacterianas habitan en comunidades complejas donde los plásmidos se diseminan entre diversas células huésped bacterianas. Por lo tanto, existe un vacío en el conocimiento sobre la persistencia de plásmidos en poblaciones bacterianas naturales. Para abordar algunas de estas lagunas en el conocimiento, el presente estudio intentó examinar los efectos del transporte de plásmidos en las etapas intrínsecas de las poblaciones bacterianas en cocultivos de Bacillus subtilis. Material y métodos: Células de B. subtilis se transformaron con vectores plasmídicos CRISPR-hCas-9 donde se examinaron las fases naturales de crecimiento bacteriano, producción de biopelículas y resistencia a los antibióticos en relación con el transporte del plásmido. Estas tres fases naturales se midieron en relación con el transporte de plásmidos a través de ensayos de cocultivo in vitro. Resultados: Después de calcular las UFC/mL, el crecimiento bacteriano en los cocultivos de B. subtilis-Carrier con Escherichia coli (B. sub-C-E. coli) y Vibrio harveyi (B. sub-C-VH) disminuyó significativamente con un -t-test de dos colas P=0. Las muestras WT B. subtilis-V.H, los cocultivos B. subtilis Carrier-V.H y los controles obtuvieron cada uno un total de 40, 47 y 46 de intensidad de biopelícula cristal violeta (CV), respectivamente. La formación de biopelículas disminuyó después de cocultivar E. coli con B. subtilis-Carrier, lo que arrojó un P<0,001 (AU)

Reducing bacterial antibiotic resistance by targeting bacterial metabolic pathways and disrupting RND efflux pump activity / Reducir la resistencia a los antibióticos bacterianos al dirigirse a las vías metabólicas bacterianas e interrumpir la actividad de la bomba de salida de RND

Antibiotic resistance is a significant issue for the medical community, worldwide. Many bacteria develop drug resistance by utilizing multidrug resistant or MDR efflux pumps that can export antibiotics from bacterial cells. Antibiotics are expelled from bacteria by efflux pumps a part of the resistance nodulation division (RND) family. Types of RND efflux pumps include the AcrAB-TolC tripartite protein pump. There are an excessive number of antibiotic compounds that have been discovered; however, only a few antibiotics are effective against MDR bacteria. Many bacteria become drug resistant when sharing genes that encode MDR efflux pump expression. MDR efflux pump encoding genes are incorporated into plasmids and then shared among bacteria. As a consequence, advancements in genetic engineering can sufficiently target and edit pathogenic bacterial genomes for perturbing drug resistance mechanisms. In this perspective and review, support will be provided for utilizing genetic modifications as an antimicrobial approach and tool that may effectively combat bacterial MDR. Ayhan et al. found that deleting acrB, acrA, and tolC increased the levels of antibiotic sensitivity in Escherichia coli. Researchers also found that glucose, glutamate, and fructose all induced the absorption of antibiotics by upregulating the gene expression of maeA and maeB that is a part of the MAL-pyruvate pathway. Therefore, the current perspective and review will discuss the potential efficacy of reducing antibiotic resistance by inhibiting genes that encode efflux protein pump expression while simultaneously upregulating metabolic genes for increased antibiotic uptake (AU)

La resistencia a los antibióticos es un problema importante para la comunidad médica en todo el mundo. Muchas bacterias desarrollan resistencia a los fármacos mediante el uso de bombas de eflujo MDR o resistentes a múltiples fármacos que pueden exportar antibióticos de las células bacterianas. Los antibióticos se expulsan de las bacterias mediante bombas de eflujo que forman parte de la familia de la división de nodulación de resistencia (RND). Los tipos de bombas de eflujo RND incluyen la bomba de proteínas tripartita AcrAB-TolC. Hay un número excesivo de compuestos antibióticos que se han descubierto; sin embargo, solo unos pocos antibióticos son eficaces contra la bacteria MDR. Muchas bacterias se vuelven resistentes a los fármacos cuando comparten genes que codifican la expresión de la bomba de eflujo MDR. Los genes que codifican la bomba de eflujo MDR se incorporan a los plásmidos y luego se comparten entre las bacterias. Como consecuencia, los avances en la ingeniería genética pueden apuntar y editar suficientemente los genomas bacterianos patógenos para perturbar los mecanismos de resistencia a los medicamentos. En esta perspectiva y revisión, se brindará apoyo para utilizar modificaciones genéticas como un enfoque y una herramienta antimicrobianos que pueden combatir eficazmente la MDR bacteriana. Ayhan y col. encontraron que la eliminación de acrB, acrA y tolC aumentaba los niveles de sensibilidad a los antibióticos en Escherichia coli. Los investigadores también encontraron que la glucosa, el glutamato y la fructosa inducían la absorción de antibióticos al regular al alza la expresión génica de maeA y maeB que es parte de la vía MAL-piruvato. Por lo tanto, la perspectiva actual y la revisión discutirán la eficacia potencial de reducir la resistencia a los antibióticos al inhibir los genes que codifican la expresión de la bomba de proteínas de salida y, al mismo tiempo, regular al alza los genes metabólicos para una mayor absorción de antibióticos (AU)