Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine.

The utilization of growth factors in the process of tissue regeneration has garnered significant interest and has been the subject of extensive research. However, despite the fervent efforts invested in recent clinical trials, a considerable number of these studies have produced outcomes that are deemed unsatisfactory. It is noteworthy that the trials that have yielded the most satisfactory outcomes have exhibited a shared characteristic, namely, the existence of a mechanism for the regulated administration of growth factors. Despite the extensive exploration of drug delivery vehicles and their efficacy in delivering certain growth factors, the development of a reliable predictive approach for the delivery of delicate growth factors like Vascular Endothelial Growth Factor (VEGF) remains elusive. VEGF plays a crucial role in promoting angiogenesis; however, the administration of VEGF demands a meticulous approach as it necessitates precise localization and transportation to a specific target tissue. This process requires prolonged and sustained exposure to a low concentration of VEGF. Inaccurate administration of drugs, either through off-target effects or inadequate delivery, may heighten the risk of adverse reactions and potentially result in tumorigenesis. At present, there is a scarcity of technologies available for the accurate encapsulation of VEGF and its subsequent sustained and controlled release. The objective of this review is to present and assess diverse categories of VEGF administration mechanisms. This paper examines various systems, including polymeric, liposomal, hydrogel, inorganic, polyplexes, and microfluidic, and evaluates the appropriate dosage of VEGF for multiple applications.

Structural parameters of nanoparticles affecting their toxicity for biomedical applications: a review.

Rapidly growing interest in using nanoparticles (NPs) for biomedical applications has increased concerns about their safety and toxicity. In comparison with bulk materials, NPs are more chemically active and toxic due to the greater surface area and small size. Understanding the NPs' mechanism of toxicity, together with the factors influencing their behavior in biological environments, can help researchers to design NPs with reduced side effects and improved performance. After overviewing the classification and properties of NPs, this review article discusses their biomedical applications in molecular imaging and cell therapy, gene transfer, tissue engineering, targeted drug delivery, Anti-SARS-CoV-2 vaccines, cancer treatment, wound healing, and anti-bacterial applications. There are different mechanisms of toxicity of NPs, and their toxicity and behaviors depend on various factors, which are elaborated on in this article. More specifically, the mechanism of toxicity and their interactions with living components are discussed by considering the impact of different physiochemical parameters such as size, shape, structure, agglomeration state, surface charge, wettability, dose, and substance type. The toxicity of polymeric, silica-based, carbon-based, and metallic-based NPs (including plasmonic alloy NPs) have been considered separately.

Step-by-Step Regulation of Productive and Abortive Transcription Initiation by Pyrophosphorolysis.

An understanding of the kinetics and mechanism of bacterial transcription initiation is needed to understand regulation of gene expression and advance fields from antibiotic discovery to promoter design. The step-by-step forward kinetics and mechanism of initiation and RNA-DNA hybrid growth, made irreversible by omitting pyrophosphate (PPi) byproduct, were determined recently for E. coli RNA polymerase (RNAP)-λPR promoter complexes. Strong position-dependences of overall rate constants (kcat/Km analogs) for each nucleotide-addition step were observed because of coupling of hybrid growth to disruption of promoter contacts, bubble closing, and RNAP escape. Here we investigate reversal of these steps (pyrophosphorolysis) at PPi concentrations ([PPi]) found in exponentially-growing cells. We quantify [PPi] effects on the amount and rate of synthesis of long (>10-mer, post-escape) and short (stalled, abortive) RNA to determine how PPi regulates initiation. Physiological [PPi] makes uridine incorporation and some other initiation steps significantly reversible. Physiological [PPi] reduces the fraction of RNAP-promoter complexes that productively initiate and the rate of RNA synthesis per productive complex, while increasing the fraction of complexes that abortively initiate, affecting abortive rates, and shifting the abortive-product distribution to shorter RNAs. Pyrophosphorolysis rates for some initiation complexes are orders of magnitude larger than for removal of the same nucleotide from elongation complexes because of the strong bias toward the pre-translocated state in initiation, and exhibit even stronger dependences on nucleotide identity (pyrimidine ≫ purine). Because cytoplasmic [PPi] is much higher in exponential-phase than stationary-phase cells, these [PPi] effects on initiation rates and amounts of RNA synthesis must be physiologically-relevant.

Impact of human papillomavirus (HPV) self-collection on subsequent cervical cancer screening completion among under-screened US women: MyBodyMyTest-3 protocol for a randomized controlled trial.

BACKGROUND: Screening substantially reduces cervical cancer incidence and mortality. More than half of invasive cervical cancers are attributable to infrequent screening or not screening at all. The current study, My Body My Test (MBMT), evaluates the impact of mailed kits for self-collection of samples for human papillomavirus (HPV) testing on completion of cervical cancer screening in low-income, North Carolina women overdue for cervical cancer screening. METHODS/DESIGN: The study will enroll at least 510 US women aged 25-64 years who report no Pap test in the last 4 years and no HPV test in the last 6 years. We will randomize participants to an intervention or control arm. The intervention arm will receive kits to self-collect a sample at home and mail it for HPV testing. In both the intervention and control arms, participants will receive assistance in scheduling an appointment for screening in clinic. Study staff will deliver HPV self-collection results by phone and assist in scheduling participants for screening in clinic. The primary outcome is completion of cervical cancer screening. Specifically, completion of screening will be defined as screening in clinic or receipt of negative HPV self-collection results. Women with HPV-negative self-collection results will be considered screening-complete. All other participants will be considered screening-complete if they obtain co-testing or Pap test screening at a study-affiliated institution or other clinic. We will assess whether the self-collection intervention influences participants' perceived risk of cervical cancer and whether perceived risk mediates the relationship between HPV self-collection results and subsequent screening in clinic. We also will estimate the incremental cost per woman screened of offering at-home HPV self-collection kits with scheduling assistance as compared to offering scheduling assistance alone. DISCUSSION: If mailed self-collection of samples for HPV testing is an effective strategy for increasing cervical cancer screening among women overdue for screening, this method has the potential to reduce cervical cancer incidence and mortality in medically underserved women at higher risk of developing cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02651883, Registered on 11 January 2016.