Lymphotoxin-ß promotes breast cancer bone metastasis colonization and osteolytic outgrowth.

Bone metastasis is a lethal consequence of breast cancer. Here we used single-cell transcriptomics to investigate the molecular mechanisms underlying bone metastasis colonization-the rate-limiting step in the metastatic cascade. We identified that lymphotoxin-ß (LTß) is highly expressed in tumour cells within the bone microenvironment and this expression is associated with poor bone metastasis-free survival. LTß promotes tumour cell colonization and outgrowth in multiple breast cancer models. Mechanistically, tumour-derived LTß activates osteoblasts through nuclear factor-κB2 signalling to secrete CCL2/5, which facilitates tumour cell adhesion to osteoblasts and accelerates osteoclastogenesis, leading to bone metastasis progression. Blocking LTß signalling with a decoy receptor significantly suppressed bone metastasis in vivo, whereas clinical sample analysis revealed significantly higher LTß expression in bone metastases than in primary tumours. Our findings highlight LTß as a bone niche-induced factor that promotes tumour cell colonization and osteolytic outgrowth and underscore its potential as a therapeutic target for patients with bone metastatic disease.

Identification and Characterization of the Glutathione S-Transferase Gene Family in Blueberry (Vaccinium corymbosum) and Their Potential Roles in Anthocyanin Intracellular Transportation.

The glutathione S-transferases (GSTs, EC 2.5.1.18) constitute a versatile enzyme family with pivotal roles in plant stress responses and detoxification processes. Recent discoveries attributed the additional function of facilitating anthocyanin intracellular transportation in plants to GSTs. Our study identified 178 VcGST genes from 12 distinct subfamilies in the blueberry genome. An uneven distribution was observed among these genes across blueberry's chromosomes. Members within the same subfamily displayed homogeneity in gene structure and conserved protein motifs, whereas marked divergence was noted among subfamilies. Functional annotations revealed that VcGSTs were significantly enriched in several gene ontology and KEGG pathway categories. Promoter regions of VcGST genes predominantly contain light-responsive, MYB-binding, and stress-responsive elements. The majority of VcGST genes are subject to purifying selection, with whole-genome duplication or segmental duplication serving as key processes that drive the expansion of the VcGST gene family. Notably, during the ripening of the blueberry fruit, 100 VcGST genes were highly expressed, and the expression patterns of 24 of these genes demonstrated a strong correlation with the dynamic content of fruit anthocyanins. Further analysis identified VcGSTF8, VcGSTF20, and VcGSTF22 as prime candidates of VcGST genes involved in the anthocyanin intracellular transport. This study provides a reference for the exploration of anthocyanin intracellular transport mechanisms and paves the way for investigating the spectrum of GST functions in blueberries.

Positive effect of microvascular proliferation on functional recovery in experimental cervical spondylotic myelopathy.

Background and purpose: Cervical Spondylotic Myelopathy (CSM), the most common cause of spinal cord dysfunction globally, is a degenerative disease that results in non-violent, gradual, and long-lasting compression of the cervical spinal cord. The objective of this study was to investigate whether microvascular proliferation could positively affect neural function recovery in experimental cervical spondylotic myelopathy (CSM). Methods: A total of 60 male adult Sprague-Dawley (SD) were randomly divided into four groups: Control (CON), Compression (COM), Angiostasis (AS), and Angiogenesis (A G),with 15 rats in each group. Rats in the AS group received SU5416 to inhibit angiogenesis, while rats in the AG group received Deferoxamine (DFO) to promote angiogenesis. Motor and sensory functions were assessed using the Basso Beattie Bresnahan (BBB) scale and somatosensory evoked potential (SEP) examination. Neuropathological degeneration was evaluated by the number of neurons, Nissl bodies (NB), and the de-myelination of white matter detected by Hematoxylin & Eosin(HE), Toluidine Blue (TB), and Luxol Fast Blue (LFB) staining. Immunohistochemical (IHC) staining was used to observe the Neurovascular Unit (NVU). Results: Rats in the CON group exhibited normal locomotor function with full BBB score, normal SEP latency and amplitude. Among the other three groups, the AG group had the highest BBB score and the shortest SEP latency, while the AS group had the lowest BBB score and the most prolonged SEP latency. The SEP amplitude showed an opposite performance to the latency. Compared to the COM and AS groups, the AG group demonstrated significant neuronal restoration in gray matter and axonal remyelination in white matter. DFO promoted microvascular proliferation, especially in gray matter, and improved the survival of neuroglial cells. In contrast, SU-5416 inhibited the viability of neuroglial cells by reducing micro vessels. Conclusion: The microvascular status was closely related to NVU remodeling an-d functional recovery. Therefore, proliferation of micro vessels contributed to function -al recovery in experimental CSM, which may be associated with NVU remodeling.