Aptamer-siRNA chimeras: Promising tools for targeting HER2 signaling in cancer.

RNA interference is a transformative approach and has great potential in the development of novel and more efficient cancer therapeutics. Immense prospects exist in the silencing of HER2 and its downstream genes which are overexpressed in many cancers, through exogenously delivered siRNA. However, there is still a long way to exploit the full potential and versatility of siRNA therapeutics due to the challenges associated with the stability and delivery of siRNA targeted to specific sites. Aptamers offer several advantages as a vehicle for siRNA delivery, over other carriers such as antibodies. In this review, we discuss the progress made in the development and applications of aptamer-siRNA chimeras in HER2 targeting and gene silencing. A schematic workflow is also provided which will provide ample insight for all those researchers who are new to this field. Also, we think that a mechanistic understanding of the HER2 signaling pathway is crucial in designing extensive investigations aimed at the silencing of a wider array of genes. This review is expected to stimulate more research on aptamer-siRNA chimeras targeted against HER2 which might arm us with potential effective therapeutic interventions for the management of cancer.

RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease.

Pathogenic viruses with an RNA genome represent a challenge for global human health since they have the tremendous potential to develop into devastating pandemics/epidemics. The management of the recent COVID-19 pandemic was possible to a certain extent only because of the strong foundations laid by the research on previous viral outbreaks, especially Ebola Virus Disease (EVD). A clear understanding of the mechanisms of the host immune response generated upon viral infections is a prime requisite for the development of new therapeutic strategies. Hence, we present here a comparative study of alterations in immune response upon SARS-CoV-2 and Ebola virus infections that illustrate many common features. Vaccination and pregnancy are two important aspects that need to be studied from an immunological perspective. So, we summarize the outcomes and immune responses in vaccinated and pregnant individuals in the context of COVID-19 and EVD. Considering the significance of immunomodulatory approaches in combating both these diseases, we have also presented the state of the art of such therapeutics and prophylactics. Currently, several vaccines against these viruses have been approved or are under clinical trials in various parts of the world. Therefore, we also recapitulate the latest developments in these which would inspire researchers to look for possibilities of developing vaccines against many other RNA viruses. We hope that the similar aspects in COVID-19 and EVD open up new avenues for the development of pan-viral therapies.

Enhanced In Vitro Wound Healing Using PVA/B-PEI Nanofiber Mats: A Promising Wound Therapeutic Agent against ESKAPE and Opportunistic Pathogens.

Opportunistic skin pathogens and their resistance to pre-existing therapeutics are a challenge to normal physiological wound healing processes. Consistent development of antimicrobial agents is required to overcome the complications raised by antimicrobial resistance. An effective alternative proposed in recent research includes the use of antimicrobial nanoparticles or nanobiopolymers. Unfortunately, metallic nanoparticles that have been proven as antimicrobial agents also possess a certain level of toxicity. In this work, we demonstrate the use of a cationic polymer, branched polyethyleneimine (B-PEI), that has been electrospun to obtain a scaffold/fiber (B-PEI NF) mat resulting in a large surface area-to-volume ratio. SEM analysis revealed that the average diameter of the obtained fibers is 240 nm. The formation of nanoscaffold modulates the controlled release of the polymer from the matrix resulting in long-term effects. The antimicrobial and antibiofilm activity of the B-PEI nanofiber (B-PEI NF) was evaluated against ESKAPE pathogens (Pseudomonas aeruginosa and Staphylococcus aureus) and also against Candida albicans. Dose-dependent inhibition was observed for microbial growth and biofilm for all three test organisms, the minimum inhibitory concentration required for inhibiting P. aeruginosa, S. aureus, and C. albicans is 33.125, 26.5, and 19.875 µM, respectively, in 2 mL of bacterial/fungal broth. Crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed significant reduction in biomass and cell viability of sessile cells, respectively, within the biofilm after treatment using B-PEI NFs. A B-PEI NF matrix promotes cell migration and wound healing processes by mimicking the extracellular matrix. In vitro wound healing studies showed a fivefold increase in cell migration and wound healing by B-PEI NFs (97% wound coverage in 17 h) when compared to B-PEI (15% wound coverage in 17 h). The in vitro wound healing assays confirmed the biocompatibility and better wound healing activity of B-PEI NF mats.