Shengui Sansheng San Ameliorates Cerebral Energy Deficiency via Citrate Cycle After Ischemic Stroke

Cerebral energy deficiency is a key pathophysiologic cascade that results in neuronal injury and necrosis after ischemic stroke. Shengui Sansheng San (SSS) has been used to treat stroke for more than 300 years. In present study, we investigated the therapeutic efficacy and mechanism of SSS extraction on cerebral energy deficiency post-stroke. In permanent middle cerebral artery occlusion (pMCAo) model of rats, it suggested that SSS extraction in dose-dependent manner improved neurological function, cerebral blood flow (CBF), 18F-2-deoxy-glucose uptake and the density and diameter of alpha smooth muscle actin (α-SMA) positive vasculature in ipsilateral area, as well as decreased infarcted volume. Meanwhile, the metabolomics study in cerebrospinal fluid (CSF) was performed by using 5-(diisopropylamino)amylamine (DIAAA) derivatization-UHPLC-Q-TOF/MS approach. Eighty-eight endogenous metabolites were identified, and mainly involved in citrate cycle, fatty acid biosynthesis, aminoacyl-tRNA biosynthesis, amino acids metabolism and biosynthesis, etc. The remarkable increase of citrate in CSF after treatment with three dosages indicated that the therapeutic mechanism of SSS extraction might be related with citrate cycle. Simultaneously, it showed that high dosage group significantly increased peripheral blood glucose level, the expressions of glucose transporter (GLUT) 1, GLUT3, and monocarboxylic acid transporter 1 (MCT1), which contributed to the transportation of glucose and lactate. By the regulations of phosphorylated pyruvate dehydrogenase E1-alpha (p-PDHA1), acetyl CoA synthetase and citrate synthetase (CS), the levels of citrate and its upstream molecules (pyruvate and acetyl CoA) in peri-infarction zone further enhanced, which ultimately caused the massive yield of adenosine triphosphate (ATP). Our study first demonstrated that SSS extraction could ameliorate cerebral energy deficiency after ischemia by citrate cycle, which is characterized by the enhancements of glucose supply, transportation, utilization, and metabolism

Ginseng-Angelica-Sansheng-Pulvis Boosts Neurogenesis Against Focal Cerebral Ischemia-Induced Neurological Deficiency

BackgroundThe traditional Chinese medicine Ginseng-Angelica-Shanseng-Pulvis (GASP) has been used to treat stroke for 300 years. This present study investigated if it can induce increases in neurogenesis following cerebral ischemic injury.MethodsRats following middle cerebral artery occlusion were orally treated with high, medium, and low doses of a standardized GASP extract.ResultsAfter 14 days, treatment with GASP improved regional blood flow and infarction volume by magnetic resonance imaging scanning, enhanced Ki67+ expression in the subventricular zone, increased brain-derived neurotrophic factor (BDNF) secretion, Nestin, and bone morphogenetic protein (BMP) 2/4 expressions in the hippocampus in a dose-dependent manner. Interestingly, low-dose treatment with GASP downregulated doublecortin and Notch1 expressions in the hippocampus, as well as upregulated glial fibrillary acidic protein expression in the subgranular zone and hairy and enhancer of split (Hes) 5 expression in the hippocampus, while treatment with middle and high doses of GASP reversed these results. Meanwhile, the consumed time was shortened in the basket test and the adhesive removal test and the spending time on exploring novel objects was prolonged by GASP treatment whose effects were more obvious at day 14 post-ischemia.ConclusionOur study demonstrates that treatment with GASP increases neurogenesis and ameliorates sensorimotor functions and recognition memory. We hypothesize that these effects are thought be mediated by an effect on the BMP2/4 pathway and Notch1/Hes5 signal. Due to its beneficial efficacy, GASP can be recognized as an alternative therapeutic agent for ischemic stroke

Dietary Histidine Requirement for Juvenile Large Yellow Croaker, Pseudosciaena crocea R.

Dietary histidine requirements for large yellow croaker (initial average weight, 6.0 ± 0.10 g) were quantified by feeding isonitrogenous (crude protein 44%) and isocaloric (20 KJ/g) amino acid test diets with graded levels of histidine [0.45% (D1), 0.66% (D2), 0.78% (D3), 0.98% (D4), 1.24% (D5) and 1.40% (D6) of dry diet]. Each diet was randomly assigned to triplicate floating sea cages (1.0 × 1.0 × 1.5 m), 60 fish/cage. At the end of the 51 day experiment, the final weight (FW) and weight gain (WG) of large yellow croaker showed a positive correlation to increasing dietary histidine content (up to 0.78%), and thereafter declined. The growth of fish fed the D6 diet was significantly lower than fish maintained on the D2 and D3 diets; however, there were no significant differences in the growth of large yellow croaker among all the dietary treatments except D6. Fish fed the D3 diet had the highest FW and WG. The shift in feed efficiency (FE) values of fish fed D1 to D5 diets increased as dietary histidine content increased, and significantly decreased in fish fed the D6 diet. Based on the second-degree polynomial regression analyses of the growth data, optimum histidine requirement for juvenile large yellow croaker was 8.7 g/kg dry diet, (18.8 g/kg–20.8 g/kg of dietary protein within 95% confidence interval)

Feasibility evaluation of fermented peanut meal to replace soybean meal in the diet of common carp (Cyprinus carpio): Growth performance, serum biochemistry, intestinal health and microflora composition

The effectiveness of soybean meal (SBM) substitution with fermented peanut meal (FPM) were appraised in common carp juveniles. A diet containing 30 % SBM was perceived as the control diet, then 25 %, 50 %, 75 % and 100 % of SBM was replaced by the FPM (FPM0, FPM25, FPM50, FPM75, FPM100 groups). Each group was fed to three replicate groups of common carp (4.83 ± 0.02 g) for 56 days. Results exhibited that FPM50 group attained the significantly higher mass gain rate and specific growth rate than those of the other groups except for FPM25, higher protein efficiency ratio and lower feed conversion rate than those of the FPM75 and FPM100 groups. The FPM50 group significantly increased the contents of serum total protein and albumin and decreased the content of serum urea nitrogen. The activity of hindgut protease was significantly enhanced in the FPM50 group. Significantly higher and lower intestinal villi height was, respectively, observed in the FPM50 and FPM100 group. The FPM50 group significantly enhanced the gene expression and activities of antioxidant enzymes in the intestine, reversely decreased the content of malonaldehyde. Significant increments in the occludin, myosin light chain kinase and claudin3 gene expressions in the FPM50 group improved the increase of intestinal permeability induced by pro-inflammatory factor related genes interleukin 1β, interleukin 6 and tumor necrosis factor α. Staphylococcus and Enterococcus in the intestine abundances were effectively suppressed in the FPM50 group, and Lactococcus became the dominant intestinal bacteria genera. The optimum substitution level was estimated to be 50.93 % and 49.89 % using broken-line regression analyses based on MGR and FCR. Overall, the soybean meal in common carp feed could be substituted up to 50 % by FBM without negative influence on growth, feed utilization and intestinal health

Predictive value of Dmax and %ΔSUVmax of 18F-FDG PET/CT for the prognosis of patients with diffuse large B-cell lymphoma

Abstract Purpose To investigate the prognosis value of a combined model based on 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) baseline and interim parameters in patients with diffuse large B-cell lymphoma (DLBCL). Methods We retrospectively analyzed the PET metabolic parameters and clinical data of 154 DLBCL patients between December 2015 and October 2020. All of these patients underwent 18F-FDG PET/CT scan before treatment and after three or four courses of chemotherapy. The optimal cut-off values for quantitative variables were determined by the receiver operating characteristic (ROC) curve. The baseline and interim PET/CT parameters, which respectively included maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax) and total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), and clinical characteristics were analyzed by chi-squared test, Kaplan-Meier survival curve, and Cox regression analysis. Results Of 154 patients, 35 exhibited disease progression or recurrence. ROC analysis revealed that baseline 18F-FDG PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax), along with interim 18F-FDG PET/CT metabolic parameters such as total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), were predictive of relapse or progression in DLBCL patients (P < 0.05). The chi-squared test showed that TMTV0, STMTV0, Dmax, SUVmax1, TMTV1, TTLG1, %ΔSUVmax, Deauville score, IPI, Ann Arbor stage, and LDH were associated with patient prognosis (P < 0.05). Multivariate Cox regression analysis showed that Dmax (P = 0.021) and %ΔSUVmax (P = 0.030) were independent predictors of prognosis in DLBCL patients. There were statistically significant differences in PFS among the three groups with high, intermediate, and low risk according to the combination model (P < 0.001). The combination model presented higher predictive efficacy than single indicators. Conclusion The combined model of baseline parameter Dmax and intermediate parameter %ΔSUVmax of 18F-FDG PET/CT improved the predictive efficacy of PFS and contributed to the risk stratification of patients, providing a reference for clinical individualization and precision treatment

Lewis-Base-Catalyzed Asymmetric [3 + 3] Annulation Reaction of Morita–Baylis–Hillman Carbonates: Enantioselective Synthesis of Spirocyclohexenes

A Lewis-base-catalyzed enantioselective [3 + 3] annulation reaction of Morita–Baylis–Hillman (MBH) carbonates with α-arylidene pyrazolinones is described, affording the pyrazolone-fused spirocyclohexenes bearing an all-carbon quaternary stereocenter in high yields with good to excellent diastereoselectivities and excellent enantioselectivities

Lewis-Base-Catalyzed Asymmetric [3 + 3] Annulation Reaction of Morita–Baylis–Hillman Carbonates: Enantioselective Synthesis of Spirocyclohexenes

A Lewis-base-catalyzed enantioselective [3 + 3] annulation reaction of Morita–Baylis–Hillman (MBH) carbonates with α-arylidene pyrazolinones is described, affording the pyrazolone-fused spirocyclohexenes bearing an all-carbon quaternary stereocenter in high yields with good to excellent diastereoselectivities and excellent enantioselectivities

Lewis-Base-Catalyzed Asymmetric [3 + 3] Annulation Reaction of Morita–Baylis–Hillman Carbonates: Enantioselective Synthesis of Spirocyclohexenes

A Lewis-base-catalyzed enantioselective [3 + 3] annulation reaction of Morita–Baylis–Hillman (MBH) carbonates with α-arylidene pyrazolinones is described, affording the pyrazolone-fused spirocyclohexenes bearing an all-carbon quaternary stereocenter in high yields with good to excellent diastereoselectivities and excellent enantioselectivities

A mutation in the <i>CACNA1C</i> gene leads to early repolarization syndrome with incomplete penetrance: A Chinese family study

<div><p>Background</p><p>Early repolarization syndrome (ERS) may be a near-Mendelian or an oligogenic disease; however, no direct evidence has been provided to support this theory.</p><p>Methods and results</p><p>We described a large Chinese family with nocturnal sudden cardiac death induced by ERS in most of the young male adults. One missense mutation (p.Q1916R) was found in the major subunit of the L-type calcium channel gene <i>CACNA1C</i> by the direct sequencing of candidate genes. A concomitant gain-of-function variant in the sodium channel gene <i>SCN5A</i> (p.R1193Q) was found to rescue the phenotype of the female <i>CACNA1C</i>-Q1916R mutation carriers, which led to the incomplete penetrance. The functional studies, via the exogenous expression approach, revealed that the <i>CACNA1C-</i>Q1916R mutation led to a decreasing L-type calcium current and the protein expression defect. The decreased calcium current produced by the mutant channel was improved by isoproterenol but exacerbated by testosterone. The effects of <i>CACNA1C-</i>Q1916R mutation and testosterone on cellular electrophysiology were further confirmed by the human ventricular action potential simulation.</p><p>Conclusions</p><p>Our results demonstrated that the loss-of-function <i>CACNA1C-</i>Q1916R mutation contributed to ERS-related sudden cardiac death, and the phenotypic incomplete penetrance was modified by the <i>SCN5A</i>-R1193Q variant and sex. These findings suggest that phenotypes of ERS are modified by multiple genetic factors, which supports the theory that ERS may be an oligogenic disease.</p></div