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Background: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. Methods: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. Results: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. Conclusions: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke. [ABSTRACT FROM AUTHOR]

Inflammatory factors play a vital role in the progression of liver cancer, although exact factors and related mechanisms still remain unclear. The present study aimed at screening inflammatory factors related to liver cancer metastasis and investigating the potential mechanism by which cancer cells are recruited. We screened and validated inflammatory factors by microarray and RT-PCR. Small interfering RNA (siRNA) and recombinant protein were used to assess CXCL5 effects on the movement of liver cancer cells (LCCs). Our screening microarray demonstrated over-expression of CXCL5 in LCCs with high metastatic potentials. CXCL5 increased LCCs migration and invasion, probably through autocrine and paracrine mechanisms. CXCL5-CXCR2 and ERK1/2 pathways could play critical roles in the regulation of LCCs migration. Our data indicates that LCCs per se may act as the producer and receptor of CXCL5 responsible for liver cancer migration and invasion. [ABSTRACT FROM AUTHOR]

Background: Mutations in the PRRT2 gene have been identified as the major cause of benign familial infantile epilepsy (BFIE), paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with paroxysmal choreoathetosis/dyskinesias (ICCA). Here, we analyzed the phenotypes and PRRT2 mutations in Chinese families with BFIE and ICCA.Methods: Clinical data were collected from 22 families with BFIE and eight families with ICCA. PRRT2 mutations were screened using PCR and direct sequencing.Results: Ninety-five family members were clinically affected in the 22 BFIE families. During follow-up, two probands had one seizure induced by diarrhea at the age of two years. Thirty-one family members were affected in the eight ICCA families, including 11 individuals with benign infantile epilepsy, nine with PKD, and 11 with benign infantile epilepsy followed by PKD. Two individuals in one ICCA family had PKD or ICCA co-existing with migraine. One affected member in another ICCA family had experienced a fever-induced seizure at 7 years old. PRRT2 mutations were detected in 13 of the 22 BFIE families. The mutation c.649_650insC (p.R217PfsX8) was found in nine families. The mutations c.649delC (p.R217EfsX12) and c.904_905insG (p.D302GfsX39) were identified in three families and one family, respectively. PRRT2 mutations were identified in all eight ICCA families, including c.649_650insC (p.R217PfsX8), c.649delC (p.R217EfsX12), c.514_517delTCTG (p.S172RfsX3) and c.1023A > T (X341C). c.1023A > T is a novel mutation predicted to elongate the C-terminus of the protein by 28 residues.Conclusions: Our data demonstrated that PRRT2 is the major causative gene of BFIE and ICCA in Chinese families. Site c.649 is a mutation hotspot: c.649_650insC is the most common mutation, and c.649delC is the second most common mutation in Chinese families with BFIE and ICCA. As far as we know, c.1023A > T is the first reported mutation in exon 4 of PRRT2. c.649delC was previously reported in PKD, ICCA and hemiplegic migraine families, but we further detected it in BFIE-only families. c.904_905insG was reported in an ICCA family, but we identified it in a BFIE family. c.514_517delTCTG was previously reported in a PKD family, but we identified it in an ICCA family. Migraine and febrile seizures plus could co-exist in ICCA families. [ABSTRACT FROM AUTHOR]