Parkinson’s disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier’s disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut–brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut–brain axis inflammation.

Diabetic nephropathy (DN) is one of the most significant complications of diabetes and is the primary cause of end-stage kidney disease. Cumulating evidence has shown that renal inflammation plays a role in the development and progression of DN, but the exact cellular mechanisms are unclear. Irregular expression of long non-coding RNAs (lncRNAs) is present in many diseases, including DN. However, the relationship between lncRNAs and inflammation in DN is unclear. In this study, we identified differentially expressed lncRNAs in DN using RNA-sequencing. Among these lncRNAs, we identified seven DN-related lncRNAs in vivo and in vitro using quantitative real-time PCR. One lncRNA in particular, Rpph1 (ribonuclease P RNA component H1), exhibited significantly increased expression. Further, over-expression or knockdown of Rpph1 was found to regulate cell proliferation and the expression of inflammatory cytokines in mesangial cells (MCs). The results revealed that Rpph1 directly interacts with the DN-related factor galectin-3 (Gal-3). Further, over-expression of Rpph1 promoted inflammation and cell proliferation through the Gal-3/Mek/Erk signaling pathway in MCs under low glucose conditions, while knockdown of Rpph1 inhibited inflammation and cell proliferation through the Gal-3/Mek/Erk pathway in MCs under high glucose conditions. These results provide new insight into the association between Rpph1 and the Gal-3/Mek/Erk signaling pathway during DN progression.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and a high propensity to metastasize. Lipid metabolism has emerged as a critical regulator of tumor progression and metastasis in other cancer types. Characterization of the lipid metabolic features of TNBC could provide important insights into the drivers of TNBC metastasis. Here, we showed that metastatic TNBC tumors harbor more unsaturated phospholipids, especially long-chain polyunsaturated fatty acids, at the sn-2 position of phosphatidylcholine and phosphatidylethanolamine compared with primary tumors. Metastatic TNBC tumors upregulated ACSL4, a long-chain polyunsaturated acyl-CoA synthetase that drives the preferential incorporation of polyunsaturated fatty acids into phospholipids, resulting in the alteration of membrane phospholipid composition and properties. Moreover, ACSL4-mediated phospholipid remodeling of the cell membrane induced lipid-raft localization and activation of integrin β1 in a CD47-dependent manner, which led to downstream focal adhesion kinase phosphorylation that promoted metastasis. Importantly, pharmacologic inhibition of ACSL4 suppressed tumor growth and metastasis and increased chemosensitivity in TNBC models in vivo. These findings indicate that ACSL4-mediated phospholipid remodeling enables TNBC metastasis and can be inhibited as a potential strategy to improve the efficacy of chemotherapy in TNBC. Significance: ACSL4 upregulation in triple-negative breast cancer alters cell membrane phospholipid composition to increase integrin β1 activation and drive metastasis, indicating that targeting ACSL4 could potentially block metastasis and improve patient outcomes.