Discovery of peptides for ligand-mediated delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia.

For cystic fibrosis patients, a lung-targeted gene therapy would significantly alleviate pulmonary complications associated with morbidity and mortality. However, mucus in the airways and cell entry pose huge delivery barriers for local gene therapy. Here, we used phage display technology to select for and identify mucus- and cell-penetrating peptides against primary human bronchial epithelial cells from cystic fibrosis patients cultured at the air-liquid interface.

Small airway brush gene expression predicts chronic lung allograft dysfunction and mortality.

Background: Chronic lung allograft dysfunction (CLAD) limits survival following lung transplant, but substantial lung damage occurs before diagnosis by traditional methods. We hypothesized that small airway gene expression patterns could identify CLAD risk before spirometric diagnosis and predict subsequent graft failure.

Methods: Candidate genes from 4 rejection-associated transcript sets were assessed for associations with CLAD or graft failure in a derivation cohort of 156 small airway brushes from 45 CLAD cases and 37 time-matched controls with >1-year stable lung function.

Implications of biosensors and nanobiosensors for the eco-friendly detection of public health and agro-based insecticides: A comprehensive review.

Biosensors, in particular nanobiosensors, have brought a paradigm shift in the detection approaches involved in healthcare, agricultural, and industrial sectors. In accordance with the global expansion in the world population, there has been an increase in the application of specific insecticides for maintaining public health and enhancing agriculture, such as organophosphates, organochlorines, pyrethroids, and carbamates. This has led to the contamination of ground water, besides increasing the chances of biomagnification as most of these insecticides are non-biodegradable.

Genetic analysis of a Fanconi anemia case revealed the presence of FANCF mutation (exon 1;469>C-T) with implications to develop acute myeloid leukemia.

Background: Fanconi anemia (FA) is a rare genetic disorder and one of the most common inherited forms of aplastic anemia. FA is an autosomal recessive or X-linked genetic disorder that is characterized by typical physical malformations and haematopoietic anomalies. In most cases of FA, patients harbor homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~ 10%), FANCD2 (3-6%) or FANCF (2%) genes in different ethnic populations, which leads to inherited bone marrow failure (IBMF).

Controlled loading of albumin-drug conjugates ex vivo for enhanced drug delivery and antitumor efficacy.

To harness the intrinsic transport properties of albumin yet improve the therapeutic index of current in situ albumin-binding prodrugs, we developed albumin-drug conjugates with a controlled loading that achieved better antitumor efficacy. Here, model drug monomethyl auristatin E (MMAE) was conjugated ex vivo to Cys34 of albumin via a cathepsin B-sensitive dipeptide linker to ensure that all drug would be bound specifically to albumin. The resulting albumin-drug conjugate with a drug to albumin ratio (DAR) of 1 (ALDC1) retained the native secondary structure of albumin compared to conjugate with a higher DAR of 3 (ALDC3).

Electrostatic driven transport enhances penetration of positively charged peptide surfaces through tumor extracellular matrix.

Drug carriers achieve poor and heterogeneous distribution within solid tumors due to limited transport through the tumor extracellular matrix (ECM). The tumor ECM forms a net negatively charged network that interacts with and hinders the transport of molecules in part due to electrostatic interactions. Traditionally, the surfaces of drug delivery systems are passivated to minimize these interactions, but the mechanism of how charge interactions impact transport and penetration within the tumor microenvironment (TME) is not well understood.

Identification of peptide coatings that enhance diffusive transport of nanoparticles through the tumor microenvironment.

In solid tumors, increasing drug penetration promotes their regression and improves the therapeutic index of compounds. However, the heterogeneous extracellular matrix (ECM) acts as a steric and interaction barrier that hinders effective transport of therapeutics, including nanomedicines. Specifically, the interactions between the ECM and surface physicochemical properties of nanomedicines (e.

Molecular analysis confirms the long-distance transport of Juniperus ashei pollen.

Although considered rare, airborne pollen can be deposited far from its place of origin under a confluence of favorable conditions. Temporally anomalous records of Cupressacean pollen collected from January air samples in London, Ontario, Canada have been cited as a new case of long-distance transport. Data on pollination season implicated Juniperus ashei (mountain cedar), with populations in central Texas and south central Oklahoma, as the nearest source of the Cupressacean pollen in the Canadian air samples.

Molecular approaches for the analysis of airborne pollen: A case study of Juniperus pollen.

Background: Pollen monitoring is a common and vital tool in the field of allergy, creating awareness in pollen sensitive individuals. Traditionally, pollen monitoring has been based on conventional microscopic counting techniques that are labor intensive and limited in the identification to the genus or family level. Molecular techniques provide an alternative approach that is less labor intensive and enable identification of any species by its genetic fingerprint.