Ginsenoside Rh1 Improves the Effect of Dexamethasone on Autoantibodies Production and Lymphoproliferation in MRL/lpr Mice

Ginsenoside Rh1 is able to upregulate glucocorticoid receptor (GR) level, suggesting Rh1 may improve glucocorticoid efficacy in hormone-dependent diseases. Therefore, we investigated whether Rh1 could enhance the effect of dexamethasone (Dex) in the treatment of MRL/lpr mice. MRL/lpr mice were treated with vehicle, Dex, Rh1, or Dex + Rh1 for 4 weeks. Dex significantly reduced the proteinuria and anti-dsDNA and anti-ANA autoantibodies. The levels of proteinuria and anti-dsDNA and anti-ANA autoantibodies were further decreased in Dex + Rh1 group. Dex, Rh1, or Dex + Rh1 did not alter the proportion of CD4+ splenic lymphocytes, whereas the proportion of CD8+ splenic lymphocytes was significantly increased in Dex and Dex + Rh1 groups. Dex + Rh1 significantly decreased the ratio of CD4+/CD8+ splenic lymphocytes compared with control. Con A-induced CD4+ splenic lymphocytes proliferation was increased in Dex-treated mice and was inhibited in Dex + Rh1-treated mice. Th1 cytokine IFN-γ mRNA was suppressed and Th2 cytokine IL-4 mRNA was increased by Dex. The effect of Dex on IFN-γ and IL-4 mRNA was enhanced by Rh1. In conclusion, our data suggest that Rh1 may enhance the effect of Dex in the treatment of MRL/lpr mice through regulating CD4+ T cells activation and Th1/Th2 balance

A Long-Lived Accretionary Process during the Amalgamation of the North China Craton: Insights from Neoarchean–Paleoproterozoic Polyphase Magmatism in the Lüliang Complex

There has been a long debate regarding the timing of the final amalgamation of the North China Craton, which is considered to have occurred either during the Neoarchean or Paleoproterozoic era. One major point of contention is whether there existed a long-lived subduction lasting through the Neoarchean to Paleoproterozoic. The Lüliang Complex contains multiphases of magmatism and thus represents the most viable region to address this controversy. In this study, we carried geochronological and geochemical analysis on the representative granitoids. Secondary ion mass spectrometry U–Pb dating revealed four distinct granitoid groups emplaced at 2531 ± 4, 2189–2173, 2027 ± 25, and 1852 ± 41 Ma, respectively. Notably, the 2531 Ma granitic gneiss was identified for the first time in this region. Based on the geochemical characteristics, the granitoids can be divided into two types. The 2531 and 2027 Ma groups display I-type features, while the 2189–2173 and 1852 Ma groups exhibit A-type geochemical affinities. Both I-type groups exhibit enrichment in Rb, depletion in Nb, Ta, and Ti, moderate fractionated REE patterns, substantial negative Eu anomalies, low Sr/Y ratios, and positive εHf(t) (+3.51 to +5.53 and +5.59 to +7.32, respectively), indicating that they were generated from partial melting of the juvenile mafic crust. In contrast, the 2189–2173 Ma granitoids belong to A2-type and were most likely generated by the partial melting of felsic rocks in the back-arc region, while the 1852 Ma granitoids belong to A1-type and were most possibly the result of partial melting of mafic-intermediate rocks during the post-collisional stage. Based on the records of A-type granitic magmatism and the ~1950 Ma peak metamorphism throughout the Trans-North China Orogen, we propose that a long-lived subduction process (2531–1950 Ma) can mostly explain the existing geological phenomena. It is likely that the subduction between the Eastern and Western Blocks should have commenced at ~2531 Ma, followed by a long-lived subduction. The two blocks ultimately collided with each other to form the North China Craton at ~1950 Ma, which triggered post-collisional exhumation and partial melting at ~1852 Ma

Reduced MLH3 Expression in the Syndrome of Gan-Shen Yin Deficiency in Patients with Different Diseases

Traditional Chinese medicine formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the characteristic genes of gan-shen Yin deficiency constitution in different diseases. Fifty primary liver cancer (PLC) patients, 94 hypertension (HBP) patients, and 100 diabetes mellitus (DM) patients were enrolled and classified into gan-shen Yin deficiency group and non-gan-shen Yin deficiency group according to the body constitution questionnaire to assess the clinical manifestation of patients. The mRNA expressions of 17 genes in PLC patients with gan-shen Yin deficiency were different from those without gan-shen Yin deficiency. However, considering all patients with PLC, HBP, and DM, only MLH3 was significantly lower in gan-shen Yin deficiency group than that in non-gen-shen Yin deficiency. By ROC analysis, the relationship between MLH3 and gan-shen Yin deficiency constitution was confirmed. Treatment of MLH3 (−/− and −/+) mice with Liuweidihuang wan, classical prescriptions for Yin deficiency, partly ameliorates the body constitution of Yin deficiency in MLH3 (−/+) mice, but not in MLH3 (−/−) mice. MLH3 might be one of material bases of gan-shen Yin deficiency constitution

Enhanced betatron radiation by steering a laser-driven plasma wakefield with a tilted shock front

We have experimentally realized a scheme to enhance betatron radiation by manipulating transverse oscillation of electrons in a laser-driven plasma wakefield with a tilted shock front (TSF). Very brilliant betatron x-rays have been produced with significant enhancement both in photon yield and peak energy but almost maintain the e-beam energy spread and charge. Particle-in-cell simulations indicate that the accelerated electron beam (e beam) can acquire a very large transverse oscillation amplitude with an increase in more than 10-fold, after being steered into the deflected wakefield due to the refraction of the driving laser at the TSF. Spectral broadening of betatron radiation can be suppressed owing to the small variation in the peak energy of the low-energy-spread e beam in a plasma wiggler regime. It is demonstrated that the e-beam generation, refracting, and wiggling can act as a whole to realize the concurrence of monoenergetic e beams and bright x-rays in a compact laser-wakefield accelerator

Enhanced Transgene Expression from Recombinant Single-Stranded D-Sequence-Substituted Adeno-Associated Virus Vectors in Human Cell Lines In Vitro and in Murine Hepatocytes In Vivo

ABSTRACT We have previously reported that the removal of a 20-nucleotide sequence, termed the D sequence, from both ends of the inverted terminal repeats (ITRs) in the adeno-associated virus serotype 2 (AAV2) genome significantly impairs rescue, replication, and encapsidation of the viral genomes (X. S. Wang, S. Ponnazhagan, and A. Srivastava, J Mol Biol 250:573–580, 1995; X. S. Wang, S. Ponnazhagan, and A. Srivastava, J Virol 70:1668–1677, 1996). Here we describe that replacement of only one D sequence in either ITR restores each of these functions, but DNA strands of only single polarity are encapsidated in mature progeny virions. Since most commonly used recombinant AAV vectors contain a single-stranded DNA (ssDNA), which is transcriptionally inactive, efficient transgene expression from AAV vectors is dependent upon viral second-strand DNA synthesis. We have also identified a transcription suppressor sequence in one of the D sequences, which shares homology with the binding site for the cellular NF-κB-repressing factor (NRF). The removal of this D sequence from, and replacement with a sequence containing putative binding sites for transcription factors in, single-stranded AAV (ssAAV) vectors significantly augments transgene expression both in human cell lines in vitro and in murine hepatocytes in vivo . The development of these genome-modified ssAAV vectors has implications not only for the basic biology of AAV but also for the optimal use of these vectors in human gene therapy. IMPORTANCE The results of the studies described here not only have provided novel insights into some of the critical steps in the life cycle of a human virus, the adeno-associated virus (AAV), that causes no known disease but have also led to the development of novel recombinant AAV vectors which are more efficient in allowing increased levels of gene expression. Thus, these studies have significant implications for the potential use of these novel AAV vectors in human gene therapy

Parameterizing starch chain-length distributions for structure-property relations

Understanding starch structure-property relationship is important for the development of new generation of starch-based foods with desirable functions. Recent developments of methodologies on the characterisation of starch molecular structures, especially how to parameterize the starch chain-length distribution (CLD) by few biologically meaningful parameters have brought new insights to explain starch physicochemical properties from molecular levels. Especially, it has shown that gelatinization temperatures are largely controlled by amylopectin short chains, while the retrogradation rate of starch molecules is controlled by amylose content, amylose short to medium chains, amylopectin external and internal chain length. Starch pasting and digestion properties are also controlled to a significant extent by its CLD. With extensive discussion of correlative and casual relations between starch CLD with its physicochemical properties, this review aims to establish a holistic starch structure-property relationship. It enables food producers to develop functional foods based on a precise understanding of starch structure-property relations

Identification of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Frequent tumor recurrence after surgery is related to its poor prognosis. Although gene expression signatures have been associated with outcome, the molecular basis of HCC recurrence is not fully understood, and there is no method to predict recurrence using peripheral blood mononuclear cells (PBMCs), which can be easily obtained for recurrence prediction in the clinical setting. Methods According to the microarray analysis results, we constructed a co-expression network using the k-core algorithm to determine which genes play pivotal roles in the recurrence of HCC associated with the hepatitis B virus (HBV) infection. Furthermore, we evaluated the mRNA and protein expressions in the PBMCs from 80 patients with or without recurrence and 30 healthy subjects. The stability of the signatures was determined in HCC tissues from the same 80 patients. Data analysis included ROC analysis, correlation analysis, log-lank tests, and Cox modeling to identify independent predictors of tumor recurrence. Results The tumor-associated proteins cyclin B1, Sec62, and Birc3 were highly expressed in a subset of samples of recurrent HCC; cyclin B1, Sec62, and Birc3 positivity was observed in 80%, 65.7%, and 54.2% of the samples, respectively. The Kaplan-Meier analysis revealed that high expression levels of these proteins was associated with significantly reduced recurrence-free survival. Cox proportional hazards model analysis revealed that cyclin B1 (hazard ratio [HR], 4.762; p = 0.002) and Sec62 (HR, 2.674; p = 0.018) were independent predictors of HCC recurrence. Conclusion These results revealed that cyclin B1 and Sec62 may be candidate biomarkers and potential therapeutic targets for HBV-related HCC recurrence after surgery.</p