高通量血液透析治疗慢性肾衰竭尿毒症的疗效及对尿毒症毒素、免疫球蛋白及肺功能指标的影响

目的:探讨高通量血液透析(HFHD)治疗慢性肾衰竭尿毒症的疗效及对尿毒症毒素、免疫球蛋白及肺功能指标的影响。方法:选取90例于2012年1月-2017年3月期间在喀什地区第一人民医院治疗的慢性肾衰竭尿毒症患者,依据随机数字表法将其分为对照组(n=45)和观察组(n=45),对照组给予血液透析滤过(HDF)治疗,观察组给予HFHD治疗,两组均透析治疗1个月。对比两组患者透析前后症状缓解情况及尿毒症毒素、免疫球蛋白及肺功能指标水平,记录两组相关并发症的发生情况。结果:透析治疗结束后观察组患者缓解率为91.11%(41/45),高于对照组的73.33%(33/45)(P0.05)。两组患者透析后血磷(P~-)、血钾(K~+)、甲状旁腺激素(PTH)、β2-微球蛋白(β2-MG)水平明显低于透析前,血钙(Ca~(2+))水平明显高于透析前(P0.05);观察组透析后K~+、Ca~(2+)、P~-等尿毒症毒素水平与对照组比较差异无统计学意义(P0.05),观察组透析后PTH、β2-MG水平明显低于对照组(P0.05)。透析后,两组患者的免疫球蛋白Ig M、Ig A、Ig G水平均较透析前上升,且观察组高于对照组(P0.05)。透析后,两组患者残气量(RV)均低于治疗前,最大肺活量(FVC)、肺活量(VC)、肺总量(TLC)均高于治疗前,且观察组RV低于对照组,FVC、VC、TLC均高于对照组(P0.05)。观察组并发症发生率为8.89%(4/45),低于对照组的24.44%(11/45)(P0.05)。结论:HFHD治疗慢性肾衰竭尿毒症能够安全有效地清除尿毒症毒素,缓解患者的临床症状,且能够提高患者的免疫功能和肺功能。     

FlashPack: Fast and Simple Preparation of Ultrahigh-performance Capillary Columns for LC-MS*

1. Download : Download high-res image (99KB)
2. Download : Download full-size image

Highlights

• •Fast and simple capillary column packing protocol.
• •Low-pressure packing at <100 bars from ultrahigh sorbent suspension concentration.
• •Sorbent particle aggregation leading to blocking of the column entrance is avoided.
• •Effective for long capillary UHPLC column packing with a wide range of sorbents.

     

Multi-species okadaic acid contamination and human poisoning during a massive bloom of Dinophysis acuminata complex in southern Brazil

On June 2016, a major bloom of Dinophysis acuminata complex was noticed over the coast of Paraná State (PR), southern Brazil, an area unprotected by any official monitoring program. Here we report the results of an extensive sampling effort that ultimately led PR authorities to issue the first State shellfish-harvesting ban due to multi-species okadaic acid (OA) contamination. During its peak, the bloom covered an area of 201 km² (∼2.0–3.5 × 54.0 km), attaining unprecedentedly high cell densities along the shallow (<15 m) continental shelf (mean 2.2 × 10⁵, maximum 2.1 × 10⁶ cells L⁻¹) and adjacent sandy beaches (mean 2.8 × 10⁵, maximum 5.2 × 10⁶ cells L⁻¹). Only OA was detected in suspension (max. 188 ng L⁻¹). Toxin levels measured in bivalves were several times greater than the regulatory limit of 160 ng g⁻¹, reaching up to 3600 ng g⁻¹ in Crassostrea gasar, by far the highest OA concentrations ever reported in oysters worldwide, 7700 ng g⁻¹ in brown mussels, Perna perna, and lower levels in clams, Anomalocardia brasiliana, and mangrove mussels, Mytella spp. Nine cases of human intoxication were officially reported and five people were hospitalized with typical symptoms of Diarrhetic Shellfish Poisoning linked to the consumption of contaminated bivalves. All bivalves quickly converted most of the OA into its esterified form, DTX-3, and eliminated the toxins only a few weeks following the bloom, with C. gasar being the slowest-detoxifying species. Lower OA levels were accumulated in zooplankton, gastropods and several novel toxin vectors, including benthic organisms such as sand dollars Mellita quinquiesperforata and the ghost-shrimp Callichirus major, which may act as a good indicator of the presence of toxins in sandy beaches, and pelagic fish species that can serve as potential alternative sources of OA to humans (Chaetodipterus faber and Mugil liza). Monitoring toxin contamination in seafood other than bivalves is thus recommended to ensure comprehensive human health protection during massive Dinophysis blooms. Additionally, since OA was also present at low concentrations in the liver of Guiana dolphins Sotalia guianensis and penguins Spheniscus magellanicus, exposure to biotoxins should be considered in conservation actions involving threatened and near-threatened marine organisms in this region.     

Trends in Dinophysis abundance and diarrhetic shellfish toxin levels in California mussels (Mytilus californianus) from Monterey Bay,California

Diarrhetic shellfish toxins (DSTs) are produced by the marine dinoflagellate, Dinophysis, as well as select species of benthic Prorocentrum. The DSTs can bioaccumulate in shellfish and cause gastrointestinal illness when humans consume high levels of this toxin. Although not routinely monitored throughout the U.S., recent studies in Washington, Texas, and New York suggest DSTs may be widespread throughout U.S. coastal waters. This study describes a four-year time series (2013–2016) of Dinophysis concentration and DST level in California mussels (Mytilus californianus) from Santa Cruz Municipal Wharf (SCMW) in Monterey Bay, California. Results show a maximum Dinophysis concentration of 9404 cells/L during this study and suggest Dinophysis persists as a member of the background phytoplankton community throughout the year. In California mussels, DSTs were found at persistent low levels throughout the course of this study, and exceeded the FDA guidance level of 160 ng/g 19 out of 192 weeks sampled. Concentrations of Dinophysis alone are a positive but weak predictor of DST level in California mussels, and basic environmental variables (temperature, salinity, and nutrients) do not sufficiently explain variation in Dinophysis concentration at SCMW. This study demonstrates that Dinophysis in Monterey Bay are producing DSTs that accumulate in local shellfish throughout the year, occasionally reaching levels of concern.     

Killer toxin-like chitinases in filamentous fungi: Structure,regulation and potential roles in fungal biology

Fungal chitinases are hydrolytic enzymes responsible for degradation of chitin. Chitinases are involved in several aspects of fungal biology, including cell wall remodelling during hyphal growth, conidial germination, autolysis, mycoparasitism and nutrient acquisition. They are divided into three distinct phylogenetic groups; A, B and C. Chitinases from the C group show structural similarities with the killer toxin zymocin produced by the yeast Kluyveromyces lactis and it is speculated that they have a similar function in filamentous ascomycetes, by facilitating penetration of toxins into cells of competing individuals. Genome analyses show that certain fungal species with a mycoparasitic lifestyle contain high numbers of killer toxin-like chitinases, compared with specialized saprotrophs and plant pathogens. Recent developments within this research field have revealed considerable variation in the modular structure and regulation of killer toxin-like chitinases, suggesting more diverse roles than merely fungal-fungal interactions. In this review, we summarize the current knowledge about this intriguing class of chitinases, including their modular structure, evolution, gene regulation, and functional analyses in mycoparasitic as well as in saprotrophic species. We also propose important questions for future research.     

A leucine zipper-based peptide hybrid delivers functional Nanog protein inside the cell nucleus

We synthesized a pair of compounds containing leucine zipper peptides to deliver protein cargo into cells. One is a cell-penetrating peptide (CPP) with Lz(E), a leucine zipper peptide containing negatively charged amino acids, and the other is a Nanog protein with Lz(K), a leucine zipper peptide containing positively charged amino acids. When cells were treated with these equimolar mixtures, Nanog-Lz(K) hybridized with Lz(E)-CPP was successfully delivered into the cells. Furthermore, Nanog-Lz(K) exerted its proper function after nuclear transport.     

Uncialamycin as a novel payload for antibody drug conjugate (ADC) based targeted cancer therapy

Uncialamycin analogs were evaluated as potential cytotoxic agents in an antibody-drug conjugate (ADC) approach to treating human cancer. These analogs were synthesized using Hauser annulations of substituted phthalides as a key step. A highly potent uncialamycin analog 3c with a valine-citrulline dipeptide linker was conjugated to an anti-mesothelin monoclonal antibody (mAb) through lysines to generate a meso-13 conjugate. This conjugate demonstrated subnanomolar potency (IC50?=?0.88?nM, H226 cell line) in in vitro cytotoxicity experiments with good immunological specificity to mesothelin-positive lung cancer cell lines. The potency and mechanism of action of this uncialamycin class of enediyne antitumor antibiotics make them attractive payloads in ADC-based cancer therapy.     

Identification of a α‐helical molten globule intermediate and structural characterization of β‐cardiotoxin,an all β‐sheet protein isolated from the venom of Ophiophagus hannah (king cobra)

β‐Cardiotoxin is a novel member of the snake venom three‐finger toxin (3FTX) family. This is the first exogenous protein to antagonize β‐adrenergic receptors and thereby causing reduction in heart rates (bradycardia) when administered into animals, unlike the conventional cardiotoxins as reported earlier. 3FTXs are stable all β‐sheet peptides with 60–80 amino acid residues. Here, we describe the three‐dimensional crystal structure of β‐cardiotoxin together with the identification of a molten globule intermediate in the unfolding pathway of this protein. In spite of the overall structural similarity of this protein with conventional cardiotoxins, there are notable differences observed at the loop region and in the charge distribution on the surface, which are known to be critical for cytolytic activity of cardiotoxins. The molten globule intermediate state present in the thermal unfolding pathway of β‐cardiotoxin was however not observed during the chemical denaturation of the protein. Interestingly, circular dichroism (CD) and NMR studies revealed the presence of α‐helical secondary structure in the molten globule intermediate. These results point to substantial conformational plasticity of β‐cardiotoxin, which might aid the protein in responding to the sometimes conflicting demands of structure, stability, and function during its biological lifetime.     

A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins

1. Download high-res image (237KB)
2. Download full-size image

     

昆虫病原线虫共生菌Tc毒素研究进展

来自昆虫病原线虫共生菌的Tc毒素是一类多亚基组成的高分子蛋白复合物,对多种农业害虫具有广谱的胃毒活性,这类毒素与目前已知的其它杀虫蛋白同源性非常低,有可能成为新的杀虫资源。本文对来自昆虫病原线虫共生菌的Tc毒素的特性、作用模式等方面的国内外研究进展进行了综述。