Leptin receptor+ cells promote bone marrow innervation and regeneration by synthesizing nerve growth factor.

The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this is regulated. Here we found that nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells is required to maintain nerve fibres in adult bone marrow. In nerveless bone marrow, steady-state haematopoiesis was normal but haematopoietic and vascular regeneration were impaired after myeloablation. LepR+ cells, and the adipocytes they gave rise to, increased NGF production after myeloablation, promoting nerve sprouting in the bone marrow and haematopoietic and vascular regeneration. Nerves promoted regeneration by activating ß2 and ß3 adrenergic receptor signalling in LepR+ cells, and potentially in adipocytes, increasing their production of multiple haematopoietic and vascular regeneration growth factors. Peripheral nerves and LepR+ cells thus promote bone marrow regeneration through a reciprocal relationship in which LepR+ cells sustain nerves by synthesizing NGF and nerves increase regeneration by promoting the production of growth factors by LepR+ cells.

Sinomenine improves renal fibrosis by regulating mesenchymal stem cell-derived exosomes and affecting autophagy levels.

BACKGROUND: This study attempts to investigate the therapeutic effect of sinomenine on renal fibrosis and its mechanism. METHODS: The 8-week-old C57BL/6 male mice were randomly divided into sham group, UUO model group, UUO sinomenine group (UUO + Sino 50), UUO + sinomenine group (UUO + Sino 100), UUO + exosome group (exo), and UUO + exo-inhibitor. The pathological changes of kidney were observed by H&E staining, the degree of renal interstitial fibrosis was detected by MASSON and Sirius red staining, and the expressions of fibrosis and autophagy markers were detected by real-time fluorescence quantitative PCR and WB. NTA and electron microscopy were used to analyze exo secretion after sinomenine treatment. RESULTS: Sinomenine could improve the progression of renal fibrosis without causing tissue damage including heart, lungs and liver. Sinomenine could promote autophagosome formation. It could promote the secretion of exosomes from bone marrow mesenchymal stem cells (BMSCs). Sinomine regulates the PI3K-AKT pathway through BMSC-exo carrying miR-204-5p, affecting autophagy level and alleviating the process of renal fibrosis. CONCLUSION: Our study suggests that sinomine could improve the progression of renal fibrosis by influencing the expression of miR-204-5p in BMSC-exo and regulating the PI3K-AKT pathway.

Prognostic and clinicopathological significance of the Prognostic Nutritional Index in patients with gastrointestinal stromal tumours undergoing surgery: a meta-analysis.

OBJECTIVES: Previous studies have investigated the prognostic value of the Prognostic Nutritional Index (PNI) in patients with gastrointestinal stromal tumours (GISTs). However, the results have been inconsistent. We performed a meta-analysis to quantitatively determine the prognostic and clinicopathological significance of PNI in GISTs. DESIGN: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Pooled HRs and 95% CIs were calculated to estimate the prognostic value of PNI in patients with GISTs. Combined ORs and corresponding 95% CIs were used to evaluate the association between the PNI and clinicopathological characteristics. DATA SOURCES: The electronic databases PubMed, Web of Science, Embase and Cochrane Library were thoroughly searched from inception to December 2021. ELIGIBILITY CRITERIA: A random-effects model or fixed-effects model was selected based on the level of heterogeneity among the included studies. RESULTS: Eight studies comprising 2307 patients were included in this meta-analysis. A low PNI was significantly associated with worse recurrence-free survival (RFS) (HR 2.02, 95% CI 1.66 to 2.47, p<0.001) and overall survival (OS) (HR 4.35, 95% CI 1.25 to 16.83, p=0.033) in patients with GISTs. In addition, a low PNI was significantly associated with tumour size ≥5 cm (OR 1.65, 95% CI 1.21 to 2.24, p=0.002) and primary tumour site in small intestine/colorectum/extra-GISTs (OR 2.03, 95% CI 1.26 to 3.26, p=0.004). CONCLUSIONS: Patients with GISTs and a lower PNI had inferior RFS and OS. Patients with GISTs and a low PNI may have a higher risk of tumour recurrence.

[Detection of a BRCA1 c.2013_2014ins GT variant an ethnic Han Chinese pedigree affected with breast cancer].

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION: The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.