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Acute pancreatitis (AP) is the acute inflammation of the pancreas. The morbidity of AP has increased in recent years. Certain patients eventually develop severe AP (SAP), which rapidly progresses to multiple organ dysfunction; the incidence of this occurring in patients with AP is 20‑30%. To date, no specific drugs or methods exist to treat this disease. Rutaecarpine relaxes vascular smooth muscle by stimulating calcitonin gene‑related peptide (CGRP) release via activation of vanilloid receptor subtype 1 (VR1). It has been demonstrated that rutaecarpine induces a therapeutic effect on SAP. The present study was conducted to characterize the molecular mechanisms underlying the protective effects of rutaecarpine against AP using a rat model of AP. Gross pathological changes of the pancreas, as well as the pancreatic tissue histopathological score, were assessed following treatment with rutaecarpine, capsazepine or a combination of the two. Serum amylase activity was detected using an automatic biochemistry analyzer. Changes in the serum concentrations of interleukin (IL)‑6, tumor necrosis factor (TNF‑α), IL‑10 and CGRP were assessed by ELISA and radioimmunoassay. The results demonstrated that pre‑treatment with rutaecarpine markedly decreased pancreatic inflammation and necrosis, reduced the volume of ascites, and significantly increased the plasma concentration of CGRP and the serum concentration of IL‑10, an anti‑inflammatory cytokine. However, serum concentrations of the inflammatory cytokines IL‑6 and TNF‑α were decreased. The effect of rutaecarpine treatment markedly improved with increases in the drug dose. Capsazepine, as a competitive vanilloid receptor antagonist, abolished these protective effects of rutaecarpine against AP. Therefore, the results of the present study indicate that rutaecarpine protects against AP in rats by upregulating endogenous CGRP release via activation VR1 of, to improving the microcirculation of the pancreatic tissue and regulate the expression of inflammatory factors. [ABSTRACT FROM AUTHOR]

Introduction We diagnosed two Chinese hereditary PC deficiency families and identified two novel compound heterozygous mutations (p.Arg194Cys/Gly324Ser and p.Glu274X/Asp297His) in the protein C ( PROC ) gene. The probands were classified as types I and II PC deficiency. The aim of this article is to access the influence of the mutations on PC activity, antigen and protein structure, and to evaluate whether there is abnormal PC localization. Materials and methods Genomic DNA of all family members was extracted, PCR amplified, and sequenced. The mutant PC expression plasmids were constructed. Expression assays, intracellular localization, and molecular modeling were performed. Results Proband 1, a type II PC defect, harbored a compound heterozygous mutation, p.Arg194Cys/Gly324Ser in the PROC gene, underwent two thromboembolic events. Expression assays indicated that the p.Arg194Cys mutant lead to decreased PC activity and normal PC Ag levels. Intracellular localization showed that both p.Arg194Cys and p.Gly324Ser co-localized with the endoplasmic reticuli and the Golgi apparatus. Molecular modeling suggested that the p.Gly324Ser mutation disturbed the interaction between the heavy and light chains of the PC protein. Proband 2, a type I PC defect, harbored a compound heterozygous PROC gene mutation, p.Glu274X/Asp297His, presented with recurrent spontaneous abortion and right popliteal vein thrombosis. Expression results were in accordance with the PC changes of the patient, and existed in defective PC transport. Structural model suggested p.Glu274X lead to disulfide bond between heavy and light chain cannot form. Conclusions Our results confirm that two novel compound heterozygous PROC gene mutations are causative on the two PC deficiency families. [ABSTRACT FROM AUTHOR]

BCR-ABL tyrosine kinase inhibitor imatinib fails to eradicate leukemia stem cells (LSCs), the underlying mechanisms maintaining CML LSCs remain poorly understood. Here, we showed that transient inhibition of miR-21 by antagomiR-21 markedly increased imatinib-induced apoptosis in CML, but not normal CD34 + stem/progenitor cells. Furthermore, PI3K inhibitors also significantly sensitized CML CD34 + cells to imatinib-induced apoptosis. MiR-21 or PI3K inhibitor in combination with imatinib treatment significantly decreased AKT phosphorylation and c-Myc expression than either agent did alone, but did not affect Bim and Bcl-6 expresssion. These findings indicate that miR-21 is required for maintaining the imatinib-resistant phenotype of CML CD34 + cells through PI3K/AKT signaling pathway, thus providing the basis for a promising therapeutic approach to eliminate CML LSCs. [ABSTRACT FROM AUTHOR]

Abstract: A 7-cm long aragonite stalagmite, FR0510-1, from Furong Cave, Chongqing, was dated by 210Pb and 230Th methods, revealing a-2000-year record of climate history under the influence of the East Asian Monsoon. The FR0510-1 record resembles Dongge Cave DA record on 10–100-year scales, but quite different from the Wanxiang Cave WX42B record, indicating that while stalagmite δ18O record represents local/regional moisture change, spatial variability of the monsoonal rainfall over eastern China must take into account. During the past 2000years, climate in Chongqing was relatively wet in the intervals of 50 BC–AD 250, AD 1150–1450 and AD 1600–1950, and relatively dry during the periods of AD 250–1150 and AD 1450–1600. Dry conditions were prevailing over the Medieval Warm Period, whereas wet climates were dominant during the most time of the Little Ice Age in Chongqing area. [Copyright &y& Elsevier]

Abstract: We select four caves and their nearby cities in the monsoonal region of China for studying the relationships among precipitation, temperature, summer monsoon intensity and stalagmite δ18O. The instrumental, historic and stalagmite δ18O records from these areas show strong spatial disparities on annual to decadal scales, so that climatic conditions in a single location cannot represent these of the entire eastern China. On time scales <500years, stronger summer monsoon may lead to higher rainfall in some locations but not over eastern China. Correlation between the summer monsoon strength and precipitation is not only location-dependent but also changes with time. One may not use the paleoclimatic pattern of cold–dry and warm–wet on glacial/interglacial ages throughout all time scales for climatic conditions in the monsoonal region. On centennial to millennial scales, stalagmite δ18O variation trend from eastern China resemble solar irradiance with lighter δ18O corresponding to increased solar irradiance, and vice versa. The similar trends may reflect climatic feedbacks link to solar forcing to cause changes in the summer monsoon intensity and/or in monsoonal circulation. Changes in monsoonal circulation and intensity affect (1) summer rainfall intensity, (2) summer/winter precipitation ratio, or (3) ratio of moisture from Indian/Pacific oceans, or a combination of the three. Thus, a speleothem δ18O record may not be proper to be used as a proxy of paleo-precipitation amount, especially on short time scales. Based on the four stalagmite δ18O records during the last 2000years, EASM strength decreased from AD 200 to AD 500, and from AD 1300 to AD 1600 (the 1st half of the Little Ice Age), whereas EASM strength increased from AD 1600 to AD 1900 (the 2nd half of the Little Ice Age). The EASM strength has weakened since early 1900’s. [Copyright &y& Elsevier]

Abstract: In this study, we aim to screen metastasis-related proteins in human lung squamous carcinoma (LSC) using laser capture microdissection and a proteomic approach. Twenty two differential proteins were identified from pooled microdissected primary LSC and matched lymph node (LN) metastatic tissues. Expression of the differential protein 14-3-3 sigma was determined by Western blotting and immunohistochemistry. In cell invasion assay, down-regulated 14-3-3 sigma by siRNA increased in vitro invasive ability of HTB-182 and A549 cells, up-regulation of 14-3-3 sigma by pcDNA3.0/14-3-3 sigma decreased in vitro invasive ability of HTB-182 and A549 cells. The data suggest that 14-3-3 sigma is a potential LN metastasis-related protein in LSC, and its dysregulation might play an important role in the LN metastatic process of LSC. [Copyright &y& Elsevier]