Design and evaluation of rhubarb total free anthraquinones oral colon-specific drug delivery granules to improve the purgative effect

Rhubarb is commonly used as a cathartic in Asian countries. However, researchers have devotedextensive concerns to the quality control and safety of rhubarb and traditional Chinese preparations composed of rhubarb due to the instable purgative effect and potential nephrotoxicity of anthraquinones. In this study, we aimed to prepare rhubarb total free anthraquinones (RTFA) oral colon-specific drug delivery granules (RTFA-OCDD-GN) to delivery anthraquinones to colon to produce purgative effect. RTFAOCDD-GN were prepared using chitosan and Eudragit S100 through a double-layer coating process and the formulation was optimized. Continuous release studies were performed in a simulated gastric fluid (pH 1.2), followed by a small-intestinal fluid (pH 6.8) and a colonic fluid (pH 7.4, containing rat cecal contents). The purgative effect test was performed in rats. The dissolution profile of RTFA-OCDD-GN showed that the accumulative dissolution rate of RTFA was about 83.0% in the simulated colonic fluid containing rat cecal contents and only about 9.0% in the simulated gastrointestinal fluids. And the RTFAOCDD-GN could produce the comparative purgative activity as rhubarb, suggesting it could deliver the free AQs to the colon. The RTFA-OCDD-GN was a useful media to enhance the purgative activity of free anthraquinones after administered orally

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Novel Miniature Culture System to Screen CO2-Sequestering Microalgae

In this study, a novel 96-well microplate swivel system (M96SS) was built for high-throughput screening of microalgal strains for CO2 fixation. Cell growth under different CO2 supply conditions (0.2, 0.4, 0.8, and 1.2 g L−1 d−1), residual nitrate, and pH value of Chlorella sp. SJTU-3, Chlorella pyrenoidosa SJTU-2, and Scenedesmus obliquus SJTU-3 were examined in the M96SS and traditional flask cultures. The dynamic data showed there was a good agreement between the systems. Two critical problems in miniature culture systems (intra-well mixing and evaporation loss) were improved by sealed vertical mixing of the M96SS. A sample screen of six microalgal species (Chlorella sp. SJTU-3, Chlorella pyrenoidosa SJTU-2, Selenastrum capricornutum, Scenedesmus obliquus SJTU-3, Chlamydomonas sajao, Dunaliella primolecta) was carried out in flasks and the M96SS. Chlamydomonas sajao appeared to be a robust performer (highest cell density: 1.437 g L−1) in anaerobic pond water with 0.8, and 1.2 g L−1 d−1 CO2. The reliability and efficiency of the M96SS were verified through a comparison of traditional flask culture, M96SS, Lukavský’s system, and a microplate shaker

Design, Synthesis, and Biological Application of Novel Photoaffinity Probes of Dihydropyridine Derivatives, BAY R3401

To explore the molecular mechanisms of BAY R3401, four types of novel photoaffinity probes bearing different secondary tags were synthesized. Their potency for glycogenolysis was evaluated in primary human liver HL-7702 cells and HepG2 cells. Probe 2d showed the best activity in primary human liver HL-7702 cells and HepG2 cells, with IC50 values of 4.45 μM and 28.49 μM, respectively. Likewise, probe 5d showed IC50 values of 6.46 μM in primary human liver HL-7702 cells and 15.29 μM in HepG2 cells, respectively. Photoaffinity labeling experiments were also performed and protein bands larger than 170 kDa were specifically tagged by probe 2d. The results suggest that the synthesized probe 2d might be a very promising tool for the isolation of the target proteins of BAY R3401

Research progress of active polypeptides of Cordyceps militaris

It is recognized at home and abroad that Cordyceps militaris is a fungus that can be edible and used for medicinal application, and also a common cordyceps taishanensis that is widely distributed and with very high medicinal value in China. Active Cordyceps militaris polypeptide has shown several highlights in its absorption mechanism, such as directly absorbed without the need for digestion, and absorbed quickly and completely, and more and more international researchers are attaching great importance to it. Physiological and pharmacological activities of Cordyceps militaris polypeptide are mainly to activate related enzyme systems, promote intermediary metabolisms or control the DNA transcription and translation, simultaneously activate the reticuloendothelial system and macrophage, promote the transformation of lymphocytes, and as a nonspecific immune enhancer and regulator, activate the immune competent cells, especially lymphocytes, lymphokines, mononuclear macrophage system and NK cells, thereby attacking the target cells to play an antitumor role, and also exerting its anti-aging, anticoagulant, hypolipidemic to enhance the immunity, improve the liver function and delay the aging. In this paper, the immunity improvement, anticancer, antioxidation and antimicrobial activities of active polypeptides from Cordyceps militaris are reviewed, in order to provide a solid theoretical help for the further development and application of active polypeptides of Cordyceps militaris

Design, Synthesis, and Use of Novel Photoaffinity Probes in Measuring the Serum Concentration of Glycogen Phosphorylase

A procedure to measure the serum concentration of glycogen phosphorylase during acute myocardial infarction is presented. This method was based on the synthesis of photoaffinity probes, and used the semiquantitative protein electrophoretic mobility shift technique. Three novel photoaffinity probes bearing different secondary tags were synthesized. Their potency was evaluated in an enzyme inhibition assay against rabbit muscle glycogen phosphorylase a (RMGPa). The inhibitory activity of probe 1 was only 100-fold less potent than the mother compound CP-320626. The photoaffinity labeling experiments were also performed, and a protein with molecular weight (MW) of about 90⁻100 kDa, which was consistent with the MW of GP, was clearly labeled by probe 1. A semiquantitative evaluation of the GP level in serum with probe 1 was also performed. The results showed that the protein band with a MW of about 90⁻100 kDa was tagged, and the concentration of the protein in serum was found to be between 25 and 50 ng/mL. Mass spectrometric analysis revealed that alpha-1,4 glucan phosphorylase (GPMM) was well-preserved in the bands

Research progress of active polypeptides of

It is recognized at home and abroad that Cordyceps militaris is a fungus that can be edible and used for medicinal application, and also a common cordyceps taishanensis that is widely distributed and with very high medicinal value in China. Active Cordyceps militaris polypeptide has shown several highlights in its absorption mechanism, such as directly absorbed without the need for digestion, and absorbed quickly and completely, and more and more international researchers are attaching great importance to it. Physiological and pharmacological activities of Cordyceps militaris polypeptide are mainly to activate related enzyme systems, promote intermediary metabolisms or control the DNA transcription and translation, simultaneously activate the reticuloendothelial system and macrophage, promote the transformation of lymphocytes, and as a nonspecific immune enhancer and regulator, activate the immune competent cells, especially lymphocytes, lymphokines, mononuclear macrophage system and NK cells, thereby attacking the target cells to play an antitumor role, and also exerting its anti-aging, anticoagulant, hypolipidemic to enhance the immunity, improve the liver function and delay the aging. In this paper, the immunity improvement, anticancer, antioxidation and antimicrobial activities of active polypeptides from Cordyceps militaris are reviewed, in order to provide a solid theoretical help for the further development and application of active polypeptides of Cordyceps militaris

Gelatin versus its two major degradation products, prolyl‐hydroxyproline and glycine, as supportive therapy in experimental colitis in mice

Gelatin is an anti‐inflammatory dietary component, and its predominant metabolites entering circulation are prolyl‐hydroxyproline (Pro‐Hyp) and glycine. We evaluated the protective effects of orally administered gelatin, glycine, and Pro‐Hyp 10:3:0.8 (w/w/w) against dextran sodium sulfate (DSS)‐induced colitis in mice. According to clinical, histological, and biochemical parameters, they exhibited significant activities in the order of gelatin < glycine < Pro‐Hyp. Gelatin prevented the DSS‐induced increase in interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) in the colon, rather than in peripheral blood. Glycine and Pro‐Hyp attenuated the DSS‐induced rise in colonic IL‐6 and TNF‐α, as well as peripheral IL‐1β, IL‐6, and TNF‐α. Hematologic results show the attenuation of DSS‐induced leukocytosis and lymphocytosis by glycine and Pro‐Hyp, rather than gelatin. These findings suggest that glycine and Pro‐Hyp constitute the material basis for gelatin's anticolitis efficacy, and they have better anticolitis activities and distinct mechanisms of action when ingested as free compounds than as part of gelatin

CircRNA itchy E3 ubiquitin protein ligase improves mitochondrial dysfunction in sepsis-induced acute kidney injury by targeting microRNA-214-3p/ATP-binding cassette A1 axis

AbstractBackground Circular RNAs (circRNAs) are promising biomarkers and therapeutic targets for acute kidney injury (AKI). In this study, we investigated the mechanism by which circRNA itchy E3 ubiquitin protein ligase (circ-ITCH) regulates sepsis-induced AKI.Methods A sepsis-induced AKI mouse model was created using LPS induction and circ-ITCH overexpression. Circ-ITCH levels were confirmed via RT-qPCR. Kidney tissue changes were examined through various stains and TUNEL. Enzyme-linked immunosorbent assay (ELISA) gauged oxidative stress and inflammation. Mitochondrial features were studied with electron microscopy. RT-qPCR and western blotting assessed mitochondrial function parameters. Using starBase, binding sites between circ-ITCH and miR-214-3p, as well as miR-214-3p and ABCA1, were predicted. Regulatory connections were proven by dual-luciferase assay, RT-qPCR, and western blotting.Results Circ-ITCH expression was downregulated in LPS-induced sepsis mice. Overexpression of circ-ITCH ameliorates indicators of renal function (serum creatinine [SCr], blood urea nitrogen [BUN], neutrophil gelatinase-associated lipocalin [NGAL], and kidney injury molecule-1 [Kim-1]), reduces renal cell apoptosis, mitigates oxidative stress markers (reactive oxygen species [ROS] and malondialdehyde [MDA]), and diminishes inflammatory markers (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF-α]). Moreover, circ-ITCH overexpression alleviated mitochondrial damage and dysfunction. Furthermore, circ-ITCH acts as a sponge for miR-214-3p, thereby upregulating ABCA1 expression. In addition, the miR-214-3p inhibitor repressed oxidative stress, inflammation, and mitochondrial dysfunction, which was reversed by circ-ITCH knockdown. Further cellular analysis in HK-2 cells supported these findings, highlighting the protective role of circ-ITCH against sepsis-induced AKI, particularly through the miR-214-3p/ABCA1 axis.Conclusion The novel circ-ITCH/miR-214-3p/ABCA1 pathway plays an essential role in the regulation of oxidative stress and mitochondrial dysfunction in sepsis-induced AKI