Jagged 2b induces intercellular signaling within somites to establish hematopoietic stem cell fate in zebrafish.

During development, the somites play a key role in the specification of hematopoietic stem cells (HSCs). In zebrafish, the somitic Notch ligands Delta-c (Dlc) and Dld, both of which are regulated by Wnt16, directly instruct HSC fate in a shared vascular precursor. However, it remains unclear how this signaling cascade is spatially and temporally regulated within somites. Here, we show in zebrafish that an additional somitic Notch ligand, Jagged 2b (Jag2b), induces intercellular signaling to drive wnt16 expression. Jag2b activated Notch signaling in segmented somites at the early stage of somitogenesis. Loss of jag2b led to a reduction in the expression of wnt16 in the somites and an HSC marker, runx1, in the dorsal aorta, whereas overexpression of jag2b increased both. However, Notch-activated cells were adjacent to, but did not overlap with, wnt16-expressing cells within the somites, suggesting that an additional signaling molecule mediates this intercellular signal transduction. We uncover that Jag2b-driven Notch signaling induces efna1b expression, which regulates wnt16 expression in neighboring somitic cells. Collectively, we provide evidence for previously unidentified spatiotemporal regulatory mechanisms of HSC specification by somites.

Incisional hernia after extreme lateral interbody fusion on the lumbar spine: A case report.

INTRODUCTION: Extreme lateral interbody fusion is a minimally invasive lateral transpsoas approach for spine surgery. We herein report a case of an incisional hernia after an extreme lateral interbody fusion on the lumbar spine that was successfully treated by laparoscopic surgery with intraperitoneal onlay mesh repair. PRESENTATION OF CASE: A 78-year-old woman was referred to our hospital with a complaint of left abdominal bulge and pain. She had undergone an extreme lateral interbody fusion for a lumbar spinal canal stenosis from L1 to L4 a year prior. Abdominal computerized tomography showed a left lumbar incisional hernia, and laparoscopic surgery was performed. The hernia orifice was sutured closed and covered with mesh. The patient was discharged five days after the operation with no complications. DISCUSSION: When performing XLIF for a spinal disorder, the muscles should be separated bluntly along their fibers to prevent muscle atrophy, and the incised fascia should be securely sutured closed. Abdominal wall incisional hernias can occur after spinal surgeries such as extreme lateral interbody fusion. CONCLUSION: Laparoscopic repair for abdominal wall incisional hernia after spine surgery is safe and feasible.

Low utilization of glucose in the liver causes diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats.

Exogenously hypercholesterolemic (ExHC) rats develop diet-induced hypercholesterolemia (DIHC) when fed with dietary cholesterol. Previously, we reported that, under the high-sucrose-diet-feeding condition, a loss-of-function mutation in Smek2 results in low activity of fatty acid synthase (FAS) followed by the shortage of hepatic triacylglycerol content in ExHC rats and the onset of DIHC. However, the relationship between the Smek2 mutation and FAS dysfunction is still unclear. Here, we focused on carbohydrate metabolism, which provides substrates for FAS, and analyzed carbohydrate and lipid metabolisms in ExHC rats to clarify how the deficit of Smek2 causes DIHC. Male ExHC and SD rats were fed high-sucrose or high-starch diets containing 1% cholesterol for 2 weeks. Serum cholesterol levels of the ExHC rats were higher, regardless of the dietary carbohydrate. Hepatic triacylglycerol levels were higher in only the SD rats fed the high-sucrose diet. Moreover, the ExHC rats exhibited a diabetes-like status and accumulation of hepatic glycogen and low hepatic mRNA levels of liver-type phosphofructokinase (Pfkl), which encodes a rate-limiting enzyme for glycolysis. These results suggest that the glucose utilization, particularly glycolysis, is impaired in the liver of ExHC rats. To evaluate how the diet with extremely low glucose affect to DIHC, ExHC.BN-Dihc2BN, a congenic strain that does not develop DIHC, and ExHC rats were fed a high-fructose diet containing 1% cholesterol for 2 weeks. The serum cholesterol and hepatic triacylglycerol levels were similar in the strains. Results of water-soluble metabolite analysis with primary hepatocytes, an increase in fructose-6-phosphate and decreases in succinate, malate and aspartate in ExHC rats, support impaired glycolysis in the ExHC rats. Thus, the Smek2 mutation causes abnormal hepatic glucose utilization via downregulation of Pfkl expression. This abnormal glucose metabolism disrupts hepatic fatty acid synthesis and causes DIHC in the ExHC rats.

Astragaloside-IV prevents acute kidney injury and inflammation by normalizing muscular mitochondrial function associated with a nitric oxide protective mechanism in crush syndrome rats.

BACKGROUND: Crush syndrome (CS) is a serious medical condition characterized by muscle cell damage resulting from decompression after compression (i.e., ischemia/reperfusion injury). A large number of CS patients develop cardiac failure, kidney dysfunction, and systemic inflammation, even when fluid therapy is administered. We evaluated whether the administration of astragaloside-IV (AS)-containing fluid improved survival by preventing kidney and muscular mitochondrial dysfunction in a rat model of CS. RESULTS: The CS model was generated by subjecting anesthetized rats to bilateral hind limb compression with a rubber tourniquet for 5 h. Rats were then randomly divided into four groups: (1) sham; (2) CS with no treatment; (3) CS with normal saline treatment; and (4) CS with normal saline + 10 mg/kg AS. AS-containing fluid improved kidney function by improving shock and metabolic acidosis in CS rats. In addition, there was a reduction in oxidative damage. The attenuation of hyperkalemia was significantly related to improving muscle injury via preventing mitochondrial dysfunction. Moreover, this mitochondria protection mechanism was related to the nitric oxide (NO) generated by activation of endothelial nitric oxide synthase, which provided an anti-oxidative and anti-inflammatory effect. CONCLUSIONS: Treatment with AS-containing fluid led to a dramatic improvement in survival following CS because of direct and indirect anti-oxidative effects in the kidney, and improvements in mitochondrial dysfunction and inflammation owing to AS acting as an NO donor in injured muscle.