Leung, G. K.-K. | Search bioRxiv

bioRxiv2025

Vitamin D attenuates TNF-α-mediated neurotoxicity and improves functional recovery in experimental intracerebral haemorrhage

While the neuroprotective effects of vitamin D (Vit-D) have been demonstrated pre-clinically in a wide range of neurologic conditions, its potential use in the treatment of spontaneous intracerebral hemorrhage (ICH) has not been fully explored. We previously reported that Vit-D could expedite hematoma clearance in experimental ICH by inducing the conversion of M1 to M2 macrophage to enhance erythrophagocytosis1,2. Here, we provide new evidence on the dose-dependent effects of Vit-D on neuronal survival and functional recovery, lending further support for the clinical testing of Vit-D in the management of ICH.

neuroscience↗

bioRxiv2017

Forward-reverse mutation cycles between stages of cancer development

Earlier, prominent occurrences of interstitial loss-of-heterozygosities (LOHs) were found in different cancers as a type of single-nucleotide-variations (SNVs), at rates far exceeding those of the commonly investigated gain-of-heterozygosities (GOHs) type of SNVs. Herein, such co-occurrences of LOHs and GOHs were confirmed in 102 cases of four cancer types analyzed with three different next-generation sequencing platforms, comparing non-tumor, paratumor, and tumor tissues with white-blood-cell controls; and in 246 pan-cancer cases of whole-genome tumor-control pairs. Unexpectedly, large numbers of SNVs enriched with CG>TG GOHs and copy-number-variations (CNVs) proximal to these GOHs were detected in the non-tumor tissues, which were extensively reversed in paratumors showing prominent TG>CG LOHs with proximal CNVs, and less so in tumors to form forward-reverse mutation cycles. Lineage effects in the reversions, likely resulting from directional selection, supported a sequential rather than parallel mode of evolution as described in a Stage Specific Populations model of cancer development.

cancer biology↗