Biology subjects

Page, T. M.

Publications and source records attributed to Page, T. M..

3 recordsLinked to original sources

bioRxiv2026

Targeted delivery of niclosamide to FRβ-expressing macrophages with engineered 2-deoxy glucose dendrimer alleviates endometriosis progression and associated hyperalgesia

Endometriosis is a chronic, incurable disease. Due to limited efficacy, high recurrence rates, and serious side effects of current treatments, development of new, targeted, non-hormonal therapies is urgently needed. We previously reported that niclosamide, an FDA-approved anthelmintic drug, attenuates endometriotic lesion growth. We further identified folate receptor-{beta} (FR{beta})-positive macrophages as contributors to disease progression. Significantly, niclosamide inhibits FR{beta}+ macrophages and reduces inflammation, innervation, and angiogenesis. To develop niclosamide as a non-hormonal and selective immune cell-targeted therapy for endometriosis, we engineered a folic acid-conjugated 2-deoxyglucose dendrimer (FA-2DG-D) using click chemistry to enable selective FR{beta}-mediated uptake. Conjugation of niclosamide to FA-2DG-D yielded a targeted nanotherapeutic (FA-2DG-D-Niclo) with enhanced aqueous solubility, controlled intracellular release, and excellent batch-to-batch reproducibility. In a mouse model of endometriosis, FA-2DG-D demonstrated lesion-specific accumulation and selective internalization by FR{beta} macrophages with minimal off-target organ retention. A single intraperitoneal dose of FA-2DG-D-Niclo (25 or 50 mg/kg/bw of niclosamide) significantly reduced FR{beta} macrophage burden, suppressed lesion number and volume, and markedly improved endometriosis-associated hyperalgesia at two weeks post-treatment. Together, these findings establish FR{beta} macrophages as a potential target in endometriosis and present FA-2DG-D-Niclo as a non-hormonal, macrophage-focused nanomedicine for precise and effective endometriosis treatment. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/704463v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@d0101corg.highwire.dtl.DTLVardef@1d1a0bborg.highwire.dtl.DTLVardef@18f9271org.highwire.dtl.DTLVardef@d76bc7_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

In vivo X-ray Computed Microtomography: A Novel Approach to Assess Coral Skeletal Construction

Scleractinian (stony) corals build reef frameworks through calcium carbonate deposition, yet all methods for assessing skeletal growth - staining, SEM, or ex vivo {micro}CT - are limited to endpoint measurements on dead specimens. Here, we utilise in vivo X-ray computed microtomography ({micro}CT) to non-destructively quantify skeletal growth in the reef-building coral Stylophora pistillata for the first time. Our in vivo {micro}CT approach applied to one individual over 16 days revealed a volume increase from [~]630 to [~]700 mm3 that can be partitioned into external vertical extension and internal lateral thickening, generating high-resolution 4D reconstructions of the evolving skeletal architecture. These measurements were consistent with established approaches but provide additional unique insights into internal growth dynamics. We demonstrate that in vivo CT enables micron-scale monitoring of calcification processes of living stony corals, thereby representing a powerful new tool to probe coral growth dynamics in the face of rapidly changing environmental conditions.

bioengineering↗

bioRxiv2021

Transcriptomic stability or lability explains sensitivity to climate stressors in coralline algae

Crustose coralline algae (CCA) are a group of calcifying red macroalgae crucial to tropical coral reefs because they form crusts that cement together the reef framework1. Previous research into the responses of CCA to ocean warming (OW) and ocean acidification (OA) have found reductions in calcification rates and survival2,3, with magnitude of effect being species-specific. Responses of CCA to OW and OA could be linked to evolutionary divergence time and/or their underlying molecular biology, the role of either being unknown in CCA. Here we show Sporolithon durum, a species from an earlier diverged lineage that exhibits low sensitivity to climate stressors, had little change in metabolic performance and did not significantly alter the expression of any genes when exposed to temperature and pH perturbations. In contrast, Porolithon onkodes, a species from a recently diverged lineage, reduced photosynthetic rates and had over 400 significantly differentially expressed genes in response to experimental treatments, with differential regulation of genes relating to physiological processes. We suggest earlier diverged CCA may be resistant to OW and OA conditions predicted for 2100, whereas taxa from more recently diverged lineages with demonstrated high sensitivity to climate stressors may have limited ability for acclimatisation.

molecular biology↗