QTL identification of grain protein concentration and its genetic correlation with starch concentration and grain weight using two populations in maize (<Emphasis Type="Italic">Zea mays</Emphasis> L.)

Protein is one of the three main storage chemical components in maize grains, and is negatively correlated with starch concentration (SC). Our objective was to analyse the influence of genetic backgrounds on QTL detection for protein concentration (PC) and to reveal the molecular genetic associations between PC and both SC and grain weight (GWP). Two hundred and eighty-four (Pop1) and 265 (Pop2) F_2:3 families were developed from two crosses between one high-oil maize inbred GY220 and two normal maize inbreds 8984 and 8622 respectively, and were genotyped with 185 and 173 pairs of SSR markers. PC, SC and GWP were evaluated under two environments. Composite interval mapping (CIM) and multiple interval mapping (MIM) methods were used to detect single-trait QTL for PC, and multiple-trait QTL for PC with both SC and GWP. No common QTL were shared between the two populations for their four and one PC QTL. Common QTL with opposite signs of effects for PC and SC/GWP were detected on three marker intervals at bins 6.07–6.08, 8.03 and 8.03–8.04. Multiple-traits QTL mapping showed that tightly-linked QTL, pleiotropic QTL and QTL having effects with opposite directions for PC and SC/GWP were all observed in Pop1, while all QTL reflected opposite effects in Pop2.     

miR‐126 reduces trastuzumab resistance by targeting PIK3R2 and regulating AKT/mTOR pathway in breast cancer cells

MicroRNAs (miRNAs) have been found to play a key role in drug resistance. In the current study, we aimed to explore the potential role of miR‐126 in trastuzumab resistance in breast cancer cells. We found that the trastuzumab‐resistant cell lines SKBR3/TR and BT474/TR had low expression of miR‐126 and increased ability to migrate and invade. The resistance, invasion and mobilization abilities of the cells resistant to trastuzumab were reduced by ectopic expression of miR‐126 mimics. In comparison, inhibition of miR‐126 in SKBR3 parental cells had the opposite effect of an increased resistance to trastuzumab as well as invasion and migration. It was also found that miR‐126 directly targets PIK3R2 in breast cancer cells. PIK3R2‐knockdown cells showed decreased resistance to trastuzumab, while overexpression of PIK3R2 increased trastuzumab resistance. In addition, our finding showed that overexpression of miR‐126 reduced resistance to trastuzumab in the trastuzumab‐resistant cells and that inhibition of the PIK3R2/PI3K/AKT/mTOR signalling pathway was involved in this effect. SKBR3/TR cells also showed increased sensitivity to trastuzumab mediated by miR‐126 in vivo. In conclusion, the above findings demonstrated that overexpression of miR‐126 or down‐regulation of its target gene may be a potential approach to overcome trastuzumab resistance in breast cancer cells.     

High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities

Cell Biology and Toxicology - Autophagy is a conserved lysosomal degradation process, and abnormal autophagy has been associated with various pathological processes, e.g., neurodegeneration,...     

Prophylactic Application of MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Prevents or Slows the Progression of Obesity,Insulin Resistance,and Cognitive Impairment in a Mouse Model of Type 2 Diabetes Mellitus

International Journal of Peptide Research and Therapeutics - Oral delivery of MA-[d-Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic...     

Cancer-associated fibroblast-derived exosomal microRNA-24-3p enhances colon cancer cell resistance to MTX by down-regulating CDX2/HEPH axis

MicroRNA-24-3p (miR-24-3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer-associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF-derived exosomal miR-24-3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF-derived exosomal miR-24-3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR-24-3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR-24-3p was verified using ChIP and dual-luciferase reporter gene assays. Exosomes were isolated from miR-24-3p inhibitor–treated CAFs (CAFs-exo/miR-24-3p inhibitor), which were used in combination with gain-of-function and loss-of-function experiments and MTX treatment. CCK-8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR-24-3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR-24-3p and could up-regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down-regulated miR-24-3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR-24-3p was transferred into CC cells via CAF-derived exosomes. CAF-derived exosomal miR-24-3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF-derived exosomal miR-24-3p accelerated resistance of CC cells to MTX by down-regulating CDX2/HEPH axis.     

HCV-specific interleukin-21+CD4+ T cells responses associated with viral control through the modulation of HCV-specific CD8+ T cells function in chronic hepatitis C patients

Interleukin-21 (IL-21)+CD4+ T cells are involved in the immune response against hepatitis B virus (HBV) by secreting IL-21. However, the role of IL-21+CD4+ T cells in the immune response against chronic hepatitis C (CHC) virus infection is poorly understood. This study aimed to investigate the role of IL-21+CD4+ T cells in CHC patients and the potential mechanisms. The study subjects included nineteen CHC patients who were grouped by viral load (low, < 10⁶ RNA copies/ml, n = 8; high, > 10⁶ RNA copies/ml, n = 11). The peripheral frequency of HCV-specific IL-21+CD4+ T cells was higher in the low viral load group and was negatively correlated with the serum HCV RNA viral load in all CHC patients. Meanwhile, IL-21+ cells accumulated in the liver in the low viral load group. In vitro, IL-21 treatment increased the expression of proliferation markers and cytolytic molecules on HCV-specific CD8+ T cells. In summary, these findings suggest that HCV-specific IL-21+CD4+ T cells might contribute to HCV control by rescuing HCV-specific CD8+ T cells in CHC patients.     

Verapamil Reverses Myocardial No-Reflow After Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

The present study evaluated the efficacy of intracoronary administration of verapamil to attenuate the no-reflow phenomenon following the primary percutaneous coronary intervention (PCI) in patients with the ST-segment elevation acute myocardial infarction (STEMI). A total of 201 patients with STEMI who underwent primary PCI within 12 h from the beginning of the heart attack were included. The no-reflow phenomenon was defined as substantial coronary anterograde flow of TIMI ≤2. Verapamil (100–200 μg) was injected into coronary artery immediately after no-reflow; the coronary arteriography was repeated later. Hundred and ninety-eight patients with STEMI successfully underwent primary PCI, and 246 stents were implanted with the average of 1.2 stents per patient. No-reflow occurred in 25 out of 198 patients (12.6 %). Twenty-one (84 %) patients developed the flow of TIMI ≥3 after intracoronary administration of verapamil, as revealed by repeated coronary angiography. Two patients developed transient hypotension which normalized without treatment within 3–5 min. Three patients showed sinus bradycardia, in one patient there was transient II sinoatrial block, and one patient developed type 1 atrioventricular block. All adverse effects were alleviated after intravenous injection of atropine (0.5–1 mg). In conclusion, the no-reflow phenomenon following primary PCI in patients with STEMI is significantly improved by intracoronary administration of verapamil which is useful to reduce cardiovascular events during operation.     

Emission and Control Characteristics for Incineration of Sedum Plumbizincicola Biomass in a Laboratory-Scale Entrained Flow Tube Furnace

Experiments were conducted to investigate and control pollutant emission from incineration of Sedum plumbizincicola plants on a laboratory scale using an entrained flow tube furnace. Without control technologies, the flue gas contained 0.101 mg Nm^?3 of Cd, 46.4 mg Nm^?3 of Zn, 553 mg Nm^?3 of NOx, 131 pg Nm^?3 of polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/Fs) and 35.4 mg Nm^?3 of polycyclic aromatic hydrocarbons (PAHs). In pollutants control experiments. Al₂O₃, CaO, and kaolin were compared as adsorbents and activated carbon was used as an end-of-pipe method for the capture of pollutants. Kaolin, the most effective of the three adsorbents, removed 91.2% of the Cd in flue gas. While 97.6% of the Cd and 99.6% of the PAHs were removed by activated carbon. Incineration may therefore be regarded as a viable option for the safe disposal of the biomass of the zinc and cadmium hyperaccumulator species S. plumbizincicola.