Gualou Xiebai Banxia decoction ameliorates Poloxamer 407-induced hyperlipidemia

Ethnopharmacological relevance: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis.Objective: The present study aimed to examine GLXBBX’s preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats.Materials and methods: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats’ plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected.Results: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1).Conclusion: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.     

Use of CC traps with different trap base colors for silverleaf whiteflies (Homoptera: Aleyrodidae), thrips (Thysanoptera: Thripidae), and leafhoppers (Homoptera: Cicadellidae)

During 1996, 1997, and 1999, studies were conducted in cotton, sugar beets, alfalfa, yardlong bean, and peanut fields to compare insect catches in CC traps equipped with different trap base colors. The studies were conducted in southwestern United States, China, and India. The nine colors, white, rum, red, yellow, lime green, spring green, woodland green (dark green), true blue, and black, varied in spectral reflectance in the visible (400-700 nm) and near-infrared (700-1050 nm) portions of spectrum. Lime green, yellow, and spring green were the three most attractive trap base colors for silverleaf whitefly, Bemisia argentifolii Bellows & Perring, and leafhopper, Empoasca spp. adults. The three trap base colors were moderately high in the green, yellow, and orange spectral regions (490-600 nm), resembling the spectral reflectance curve of the abaxial (underleaf) surfaces of green cotton leaves. True blue and white were the most attractive trap base colors for western flower thrips, Frankliniella occidentalis (Pergande), adults. The true blue and white trap bases were moderately high in the blue spectral region (400-480 nm).     

Fluctuations of transfer RNAs between classical and hybrid states

Adjacent transfer RNAs (tRNAs) in the A- and P-sites of the ribosome are in dynamic equilibrium between two different conformations called classical and hybrid states before translocation. Here, we have used single-molecule fluorescence resonance energy transfer to study the effect of Mg(2+) on tRNA dynamics with and without an acetyl group on the A-site tRNA. When the A-site tRNA is not acetylated, tRNA dynamics do not depend on [Mg(2+)], indicating that the relative positions of the substrates for peptide-bond formation are not affected by Mg(2+). In sharp contrast, when the A-site tRNA is acetylated, Mg(2+) lengthens the lifetime of the classical state but does not change the lifetime of the hybrid state. Based on these findings, the classical state resembles a state with direct stabilization of tertiary structure by Mg(2+) ions whereas the hybrid state resembles a state with little Mg(2+)-assisted stabilization. The antibiotic viomycin, a translocation inhibitor, suppresses tRNA dynamics, suggesting that the enhanced fluctuations of tRNAs after peptide-bond formation drive spontaneous attempts at translocation by the ribosome.     

Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells

Glutamate, a major excitatory neurotransmitter in the CNS, plays a critical role in neurological disorders such as stroke and Parkinson's disease. Recent studies have suggested that glutamate excess can result in a form of cell death called glutamate-induced oxytosis. In this study, we explore the protective effects of necrostatin-1 (Nec-1), an inhibitor of necroptosis, on glutamate-induced oxytosis. We show that Nec-1 inhibits glutamate-induced oxytosis in HT-22 cells through a mechanism that involves an increase in cellular glutathione (GSH) levels as well as a reduction in reactive oxygen species production. However, Nec-1 had no protective effect on free radical-induced cell death caused by hydrogen peroxide or menadione, which suggests that Nec-1 has no antioxidant effects. Interestingly, the protective effect of Nec-1 was still observed when cellular GSH was depleted by buthionine sulfoximine, a specific and irreversible inhibitor of glutamylcysteine synthetase. Our study further demonstrates that Nec-1 significantly blocks the nuclear translocation of apoptosis-inducing factor (a marker of caspase-independent programmed cell death ) and inhibits the integration of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (a pro-death member of the Bcl-2 family) into the mitochondrial membrane. Taken together, these results demonstrate for the first time that Nec-1 prevents glutamate-induced oxytosis in HT-22 cells through GSH related as well as apoptosis-inducing factor and Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-related pathways.     

Tissue- and nuclear receptor-specific function of the C-terminal LXXLL motif of coactivator NCoA6/AIB3 in mice

Although the LXXLL motif of nuclear receptor (NR) coactivators is essential for interaction with NRs, its role has not been assessed in unbiased animal models. The nuclear receptor coactivator 6 (NCoA6; also AIB3, PRIP, ASC-2, TRBP, RAP250, or NRC) is a coactivator containing an N-terminal LXXLL-1 (L1) and a C-terminal L2. L1 interacts with many NRs, while L2 interacts with the liver X receptor α (LXRα) and the estrogen receptor α (ERα). We generated mice in which L2 was mutated into AXXAL (L2m) to disrupt its interaction with LXRα and ERα. NCoA6^L2m/L2m mice exhibited normal reproduction, mammary gland morphogenesis, and ERα target gene expression. In contrast, when treated with an LXRα agonist, lipogenesis and the LXRα target gene expression were significantly reduced in NCoA6^L2m/L2m mice. The induction of Cyp7A1 expression by a high-cholesterol diet was impaired in NCoA6^L2m/L2m mice, which reduced bile acid synthesis in the liver and excretion in the feces and resulted in cholesterol accumulation in the liver and blood. These results demonstrate that L2 plays a tissue- and NR-specific role: it is required for NCoA6 to mediate LXRα-regulated lipogenesis and cholesterol/bile acid homeostasis in the liver but not required for ERα function in the mammary gland.     

Interaction of deoxyhemoglobin with the cytoplasmic domain of murine erythrocyte band 3

The partial pressure of oxygen constitutes an important factor in the regulation of human erythrocyte physiology, including control of cell volume, membrane structure, and glucose metabolism. Because band 3 is thought to be involved in all three processes and because binding of hemoglobin (Hb) to the cytoplasmic domain of band 3 (cdb3) is strongly oxygen-dependent, the possibility that the reversible association of deoxyhemoglobin (deoxyHb) with cdb3 might constitute an O(2)-dependent sensor that mediates O(2)-regulated changes in erythrocyte properties arises. While several lines of evidence support this hypothesis, a major opposing argument lies in the fact that the deoxyHb binding sequence on human cdb3 is not conserved. Moreover, no effect of O(2) pressure on Hb-band 3 interactions has ever been demonstrated in another species. To explore whether band 3-Hb interactions might be widely involved in O(2)-dependent regulation of erythrocyte physiology, we undertook characterization of the effect of O(2) on band 3-Hb interactions in the mouse. We report here that murine band 3 binds deoxyHb with significantly greater affinity than oxyHb, despite the lack of significant homology within the deoxyHb binding sequence. We further map the deoxyHb binding site on murine band 3 and show that deletion of the site eliminates deoxyHb binding. Finally, we identify mutations in murine cdb3 that either enhance or eliminate its affinity for murine deoxyHb. These data demonstrate that despite a lack of homology in the sequences of both murine band 3 and murine Hb, a strong oxygen-dependent association of the two proteins has been conserved.     

Quantifying multiple pressure interactions affecting populations of a recreationally and commercially important freshwater fish

The expanding human global footprint and growing demand for freshwater have placed tremendous stress on inland aquatic ecosystems. Aichi Target 10 of the Convention on Biological Diversity aims to minimize anthropogenic pressures affecting vulnerable ecosystems, and pressure interactions are increasingly being incorporated into environmental management and climate change adaptation strategies. In this study, we explore how climate change, overfishing, forest disturbance, and invasive species pressures interact to affect inland lake walleye (Sander vitreus) populations. Walleye support subsistence, recreational, and commercial fisheries and are one of most sought‐after freshwater fish species in North America. Using data from 444 lakes situated across an area of 475 000 km² in Ontario, Canada, we apply a novel statistical tool, R‐INLA, to determine how walleye biomass deficit (carrying capacity—observed biomass) is impacted by multiple pressures. Individually, angling activity and the presence of invasive zebra mussels (Dreissena polymorpha) were positively related to biomass deficits. In combination, zebra mussel presence interacted negatively and antagonistically with angling activity and percentage decrease in watershed mature forest cover. Velocity of climate change in growing degree days above 5°C and decrease in mature forest cover interacted to negatively affect walleye populations. Our study demonstrates how multiple pressure evaluations can be conducted for hundreds of populations to identify influential pressures and vulnerable ecosystems. Understanding pressure interactions is necessary to guide management and climate change adaptation strategies, and achieve global biodiversity targets.     

N-terminal sequence of porcine big gastrin: Sequence, synthesis, and immunochemical studies

The synthesis of fragments corresponding to the N-terminal region of porcine big gastrin is described. Radioimmunoassay using synthetic peptides supports the revised structure for the hormone.     

Overexpression of microRNA-23a-5p induces myocardial infarction by promoting cardiomyocyte apoptosis through inhibited of PI3K/AKT signalling pathway

Myocardial infarction (MI) leads to cardiac remodelling and heart failure. Cardiomyocyte apoptosis is considered a critical pathological phenomenon accompanying MI, but the pathogenesis mechanism remains to be explored. MicroRNAs (miRs), with the identity of negative regulator of gene expression, exist as an important contributor to apoptosis. During the experiment of this study, MI mice models were successfully established and sequencing data showed that the expression of miR-23a-5p was significantly enhanced during MI progression. Further steps were taken and it showed that apoptosis of cardiac cells weakened as miR-23a-5p was downregulated and on the contrary that apoptosis strengthened with the overexpression of miR-23a-5p. To explore its working mechanisms, bioinformatics analysis was conducted by referring to multi-databases to predict the targets of miR-23a-5p. Further analysis suggested that those downstream genes enriched in several pathways, especially in the PI3K/Akt singling pathway. Furthermore, it demonstrated that miR-23a-5p was negatively related to the phosphorylation of PI3K/Akt, which plays a critical role in triggering cell apoptosis during MI. Recilisib-activated PI3K/Akt singling pathway could restrain apoptosis from inducing miR-23a-5p overexpression, and Miltefosine-blocked PI3K/Akt singling pathway could restrict apoptosis from inhibiting miR-23a-5p reduction. In conclusion, these findings revealed the pivotal role of miR-23a-5p-PI3K/Akt axis in regulating apoptosis during MI, introducing this novel axis as a potential indicator to detect ischemic heart disease and it could be used for therapeutic intervention.