In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days.

Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor.

Background: Levels of sulfated Dehydroepiandrosterone (DHEA-S) are unknown in people with Cystic Fibrosis (pwCF). DHEA-S is reported to have an inverse association with inflammation and warrants evaluation in pwCF.

Methods: We compared differences in DHEA-S and other hormones between pwCF (n = 180) and without CF (n = 180) and DHEA-S association with percent predicted forced expiratory volume in one second (ppFEV1).

Evaluation of an association between RANKL and OPG with bone disease in people with cystic fibrosis.

Background: As people with Cystic Fibrosis (CF) live longer, extra-pulmonary complications such as CF-related bone disease (CFBD) are becoming increasingly important. The etiology of CFBD is poorly understood but is likely multifactorial. Bones undergo continuous remodeling via pathways including RANK (receptor activator of NF-κB)/sRANKL (soluble ligand)/OPG (osteoprotegerin).

Multidrug-resistant from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime-avibactam.

Purpose: Ceftazidime-avibactam is a novel antimicrobial combining a third-generation cephalosporin with a non-β-lactam β-lactamase inhibitor that was recently approved to treat Gram-negative hospital- and ventilator-acquired pneumonia. The use of ceftazidime-avibactam to treat respiratory infections in patients with cystic fibrosis (CF) has not been evaluated. In this study, we assessed the ceftazidime-avibactam susceptibility of multidrug-resistant (MDR) sputum isolates from adults with CF.

17β-Estradiol Dysregulates Innate Immune Responses to Pseudomonas aeruginosa Respiratory Infection and Is Modulated by Estrogen Receptor Antagonism.

Females have a more severe clinical course than males in terms of several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly in the setting of infection. Sex hormones have been implicated in experimental and clinical studies; however, immune mechanisms responsible for this sex-based disparity are unknown and the specific sex hormone target for therapeutic manipulation has not been identified.

A-single spermatogonia heterogeneity and cell cycles synchronize with rat seminiferous epithelium stages VIII-IX.

In mammalian testes, "A-single" spermatogonia function as stem cells that sustain sperm production for fertilizing eggs. Yet, it is not understood how cellular niches regulate the developmental fate of A-single spermatogonia. Here, immunolabeling studies in rat testes define a novel population of ERBB3(+) germ cells as approximately 5% of total SNAP91(+) A-single spermatogonia along a spermatogenic wave.

Cellular ontogeny of RBMY during human spermatogenesis and its role in sperm motility.

The Y-chromosome-encoded gene RBMY (RNA-binding motif on Y) is a male germline RNA-binding protein and is postulated to be a RNA-splicing regulator. In order to understand the roles of RBMY in different stages of male gamete maturation, the present study aimed at determining its cellular expression during spermatogenesis, spermeogenesis and in mature spermatozoa. In the spermatogonia (cKIT-positive cells), RBMY immunolocalized as two distinct foci, one in the nucleolus and the other in the subnuclear region; in the spermatocytes (cKIT-negative cells), the nucleus had punctuate staining with a subnuclear foci; in the pachytene cells, the protein was localized as a punctuate pattern in the nucleus spread along the elongating chromosomes.

Altered expression of progesterone receptors in testis of infertile men.

Progesterone has been implicated in the process of spermatogenesis. This study aimed to investigate the association of progesterone receptor (PR) expression with spermatogenesis in the testis of infertile men. PR mRNA and protein were assessed by in-situ hybridization and immunohistochemistry in testicular biopsies obtained from 18 infertile men.

Clinical and laboratory evaluation of idiopathic male infertility in a secondary referral center in India.

The genetic basis of infertility has received increasing recognition in recent years, particularly with the advent of assisted reproductive technology. It is now becoming obvious that genetic etiology for infertility is an important cause of disrupted spermatogenesis. Y-chromosome microdeletions and abnormal karyotype are the two major causes of altered spermatogenesis.