Biology subjects

Crofford, L.

Publications and source records attributed to Crofford, L..

2 recordsLinked to original sources

bioRxiv2026

Urobiome Analysis in Interstitial Cystitis/Bladder Pain Syndrome Reveals Nuanced Differences Associated with Localized Pain

PurposeInterstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent chronic pain syndrome associated with functional urinary disorders. IC/BPS symptoms can be localized to the pelvic-region or have co-occurring widespread pain. Importantly, response to treatment depends on pain localization phenotype. The etiology of IC/BPS remains elusive, and whether bacteria contribute to IC/BPS pathophysiology remains uncertain. Materials and MethodsWe used urine samples collected from a longitudinal randomized controlled trial of individuals with IC/BPS to study the association of the urobiome and IC/BPS symptoms over time. Individuals provided urine samples at baseline, post-treatment, and at five months. We performed a secondary analysis on urine samples applying 16S rRNA sequencing and assigned bacterial taxonomy to amplicon sequence variants (ASVs) to characterize the urobiome. We then compared urobiome bacterial diversity, stability, and its association with IC/BPS symptoms over time. We also assessed the relationship between pain localization and the urobiome. ResultsAs validation of this dataset, we noted a strong influence of menopausal status and recent urinary tract infection on the composition of the urobiome. We did not detect widespread differences in the urobiome that correlated with subjects pain localization or severity. Instead, we observed specific bacterial sequences that were altered in abundance in relation to symptomatology, such as reduced abundance of a Dialister ASV in persons with localized pelvic pain. ConclusionsTogether, this dataset advances our understanding of the urobiome in interstitial cystitis/bladder pain syndrome and sets the stage for future studies on the urobiome and interstitial cystitis/bladder pain syndrome symptoms.

microbiology↗

bioRxiv2023

Albumin-binding RNAi Conjugate for Carrier Free Treatment of Arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are joint diseases that are associated with pain and lost quality of life. No disease modifying OA drugs are currently available. RA treatments are better established but are not always effective and can cause immune suppression. Here, an MMP13-selective siRNA conjugate was developed that, when delivered intravenously, docks onto endogenous albumin and promotes preferential accumulation in articular cartilage and synovia of OA and RA joints. MMP13 expression was diminished upon intravenous delivery of MMP13 siRNA conjugates, consequently decreasing multiple histological and molecular markers of disease severity, while also reducing clinical manifestations such as swelling (RA) and joint pressure sensitivity (RA and OA). Importantly, MMP13 silencing provided more comprehensive OA treatment efficacy than standard of care (steroids) or experimental MMP inhibitors. These data demonstrate the utility of albumin hitchhiking for drug delivery to arthritic joints, and establish the therapeutic utility of systemically delivered anti-MMP13 siRNA conjugates in OA and RA. Editorial summaryLipophilic siRNA conjugates optimized for albumin binding and "hitchhiking" can be leveraged to achieve preferential delivery to and gene silencing activity within arthritic joints. Chemical stabilization of the lipophilic siRNA enables intravenous siRNA delivery without lipid or polymer encapsulation. Using siRNA sequences targeting MMP13, a key driver of arthritis-related inflammation, albumin hitchhiking siRNA diminished MMP13, inflammation, and manifestations of osteoarthritis and rheumatoid arthritis at molecular, histological, and clinical levels, consistently outperforming clinical standards of care and small molecule MMP antagonists.

bioengineering↗