Recombinant fibroblast growth factor 4 ameliorates axonal regeneration and functional recovery in acute spinal cord injury through altering microglia/macrophage phenotype.

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant fibroblast growth factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis. However, it remains to be explored whether or not rFGF4 has a neuroprotective effect for restoring neurological disorders, such as SCI. Here, we identified that rFGF4 could polarize microglia/macrophages into the restorative M2 subtype, thus exerting an anti-inflammatory effect to promote neurological functional recovery and nerve fiber regeneration after SCI. Importantly, these effects by rFGF4 were related to triggering PI3K/AKT/GSK3ß and attenuating TLR4/NF-κB signaling axes. Conversely, gene silencing of the PI3K/AKT/GSK3ß signaling or pharmacological reactivation of the TLR4/NF-κB axis aggravated inflammatory reaction. Thus, our findings highlight rFGF4 as a potentially therapeutic regulator for repairing SCI, and its outstanding effect is associated with regulating macrophage/microglial polarization.

Rhodium-Catalyzed Dehydrogenative Cycloisomerization of Dienylcyclopropane to Highly Substituted Toluene.

A rhodium-catalyzed dehydrogenative cycloisomerization of dienylcyclopropane compounds is reported, which provides a straightforward approach to a variety of highly substituted toluene derivatives in 67-85% yields. The dienylcyclopropane-imides are produced by a single-step formal three-component olefination procedure. Preliminary mechanistic studies indicated that an electron-withdrawing group as R plays a critical role in completing this transformation.

lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p.

Sorafenib (SOR) resistance remains a major obstacle in the effective treatment of hepatocellular carcinoma (HCC). A number of long noncoding RNAs (lncRNAs) are responsible for this chemoresistance. This study aimed to reveal the essential function of a recently defined lncRNA, lncRNA-POIR, in the epithelial-mesenchymal transition (EMT) and SOR sensitivity of HCC cells. SOR-induced cytotoxicity was analyzed via cell counting kit-8 and ethynyl-2'-deoxyuridine incorporation assays, whereas immunoblotting and confocal immunofluorescence were used to determine the expression levels of EMT markers. Furthermore, loss- or gain-of-function approaches were used to demonstrate the role of lncRNA-POIR/miR-182-5p on EMT and SOR sensitivity in HCC. The direct interaction between lncRNA-POIR and miR-182-5p was verified using a luciferase reporter assay. We found that knockdown of lncRNA-POIR sensitized HCC cells to SOR and simultaneously reversed EMT. As expected, miR-182-5p was confirmed as the downstream target of lncRNA-POIR. Moreover, miR-182-5p overexpression clearly reversed EMT and promoted SOR-induced cytotoxicity in representative HCC cells, whereas miR-182-5p downregulation played a contrasting role; miR-182-5p knockdown abolished the modulatory effects of lncRNA-POIR siRNA on EMT and SOR sensitivity. Together, these pieces of data suggest that lncRNA-POIR promotes EMT progression and suppresses SOR sensitivity simultaneously by sponging miR-182-5p. Thus, we proposed a compelling rationale for the use of lncRNA-POIR as a promising predictor of SOR response and as a potential therapeutic target for HCC treatment in the future.

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China].

OBJECTIVE: To explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC). METHODS: Between April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC. RESULTS: Among 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection. CONCLUSIONS: The mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.

[Effect of SSU1 multi-copy expression on Saccharomyces cerevisiae sulphite production].

OBJECTIVE: Sulfite, an intermediate metabolite in yeast sulfur-containing amino acid biosynthesis pathway, plays an important role in beer flavor stabilizing because of its antioxidant activity. In Saccharomyces cerevisiae, excretion of sulfite is regulated by sulfite transporter protein Ssulp which is encoded by SSU1. We constructed a high sulfite excreting brewing yeast strain to solve the beer staling problem by SSU1 gene over-expressing. METHODS: Sulfite transporter gene SSU1-1 and SSUJ-2 that contain different length of 5'untranslated region were cloned by PCR, with the genomic DNA of an industrial mutant strain M8 as template. The amplified DNA was digested with BamH I and Sal I, and then inserted into plasmid YEp352 digested by BamH I -Sal I and constructed the expression vector pSU1 and pSU2. pSU1 and pSU2 were transformed into laboratory strain YS58 and tested the effect of SSU1 multi-copy expression on Saccharomyces cerevisiae sulfite production. Furthermore, pSU2 was transformed into industrial brewing yeast mutant strain M8, and SO2, H2S production and beer antioxidant abilities of transformant Y2, screened out by sulfite resistance plate, were tested. RESULT: The SO2 production of laboratory yeast transformants pSU1-4 and pSU2-3 enhanced remarkably, but H2S production remained unchanged. Compared with the S. cerevisiae M8, SO2 production of transformant Y2 increased by 74.4%, TBA value decreased by 14.9%, DPPH radical scavenging ratio enhanced by 38.2%, but H2S production had little change. CONCLUSION: Over-expression of SSU1 in both laboratory S. cerevisiae strain and industrial brewing yeast strain increased their sulphite excretion, enhanced beer antioxidant abilities and had no negative effect on sulfur-containing amino acids biosynthesis.