脱乙酰化反应条件对壳聚糖性能的影响

本文研究了甲壳素在脱乙酰化反应时不同反应条件,如碱浓度、反应时间、反应温度和处理方法对壳聚糖性能,如分子量、脱乙酰化度的影响,探讨了分子主链降解反应与脱乙酰化反应之间的关系。结果表明:随着碱浓度和反应时间的增加,壳聚糖脱乙酰化度提高,而分子量降低;脱乙酰化越高,主链降解程度增加;反应温度升高,脱乙酰化反应速度加快;而采用短时重复多次反应的处理方法,则可增加壳聚糖的脱乙酰化度,并减少主链降解程度。     

Role of proteasomes in the formation of neurofilamentous inclusions in spinal motor neurons of aluminum‐treated rabbits

We examined the role of the 20S proteasome in pathologic changes, including abnormal aggregation of phosphorylated neurofilaments, of spinal motor nerve cells from aluminum‐treated rabbits. Immunohistochemistry for the 20S proteasome revealed that many lumbar spinal motor neurons without intracytoplasmic neurofilamentous inclusions or with small inclusions were more intensely stained in aluminum‐treated rabbits than in controls, whereas the immunoreactivity was greatly decreased in some enlarged neurons containing large neurofilamentous inclusions. Proteasome activity in whole spinal cord extracts was significantly increased in aluminum‐treated rabbits compared with controls. Furthermore, Western blot analysis indicated that the 20S proteasome degraded non‐phosphorylated high molecular weight neurofilament (neurofilament‐H) protein in vitro. These results suggest that aluminum does not inhibit 20S proteasome activity, and the 20S proteasome degrades neurofilament‐H protein. We propose that abnormal aggregation of phosphorylated neurofilaments is induced directly by aluminum, and is not induced by the proteasome inhibition in the aluminum‐treated rabbits. Proteasome activation might be involved in intracellular proteolysis, especially in the earlier stages of motor neuron degeneration in aluminum‐treated rabbits.     

城市污水致突变物活性及其土壤净化

城市污水及处理出水均程度不同地含有致突物质,其含量在枯水期高于丰水期。污灌区浅层地下水浓集物呈致突变性,而季节变化与原污水同步。浅层地下水GC/MS检测出31种有机化合物,基本与污水一致。实验证明土壤微生物对污水致突物有一定的降解作用。为避免污灌区浅层地下水的污染,污水在灌溉之前必须加强处理,使减少致突物至土壤降解能力所能承受的程度。     

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor

We investigated the effect of the lgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with ¹²⁵l-α-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the lgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by lgG from patients with generalized MG whose antibody titers were in the normal range and by lgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG. © 1993 John Wiley & Sons, Inc.     

Oral Controlled Release Technology for Peptides: Status and Future Prospects

In spite of significant efforts in academic and commercial laboratories, major breakthroughs in oral peptide and protein formulation have not been achieved. The major barriers to developing oral formulations for peptides and proteins include poor intrinsic permeability, lumenal and cellular enzymatic degradation, rapid clearance, and chemical and conformational stability. Pharmaceutical approaches to address these barriers, which have been successful with traditional, small, organic drug molecules, have not readily translated into effective peptide and protein formulations. The success achieved by Sandoz with cyclosporin formulations remains one clear example of what can be achieved, although it is likely that effective oral formulations for peptides and proteins will remain highly compound specific. Although the challenges are significant, the potential therapeutic benefit remains high, particularly with the increasing identification of potential peptide and protein drug candidates emerging from the biotechnology arena. Successful formulations will most likely require a systematic and careful merger of formulation and design delivery systems which maximize the potential for absorption across the epithelial cell layer.     

不同孕期阶段孕妇凝血四项及FDP和D-二聚体的变化及临床意义

目的:研究不同孕期阶段(早、中、晚)孕妇凝血四项、血浆纤维蛋白(原)降解产物[plasma fibrin/fibrinogen degradation products, FDP]、D-二聚体的变化及临床意义,为临床诊疗提供理论支持。方法:回顾性分析2021年1月至2021年12月200例孕妇就诊资料中的凝血四项,纤维蛋白原(fibrinogen, FIB)、凝血酶原时间(prothrombin time, PT)、凝血酶时间(thrombin time, TT)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)。并对FDP与D-二聚体的检测结果进行统计分析,比较孕早期、中期、晚期三个阶段凝血四项、FDP和D-二聚体水平的变化。结果:孕早期、孕中期与孕晚期PT水平比较,差异有统计学意义(P<0.05);孕早期、孕中期与孕晚期三个阶段的TT相比,差异无统计学意义(P>0.05);孕早期的APTT明显长于中期、晚期孕妇,差异有统计学意义(P<0.05);孕早期、中期、晚期孕妇,随着孕周的增加,FIB水平逐渐升高...     

Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin)

We have investigated the effect of the immunomodulator ubenimex (hereafter referred to as bestatin) on the enzymatic degradation of the extracellular matrix by human renal cell carcinoma SN12M cells during the invasive process. The invasion of SN12M cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell adhesion and migration to the extracellular matrices which may be involved in tumor cell invasion. Bestatin inhibited the degradation of type IV collagen by tumor cells, but not by tumor-conditioned medium (TCM), in a concentration-dependent manner. We also found that bestatin inhibited hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Since bestatin was found to inhibit aminopeptidase activity, the inhibition of tumor invasion by bestatin is likely to be associated with its action as an enzyme inhibitor. Bestatin only slightly inhibited tumor cell plasmin activity, which can lead to the conversion of the latent collagenase to the active form, but this slight effect was not significant. The zymography of TCM from SN12M cells showed that the treatment of tumor cells with bestatin resulted in the disappearance of the 68 kDa type IV collagenase-enzyme level (active form) and slight reduction of the 72 kDa type IV collagenase-enzyme level (latent form). These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells, suggesting that the aminopeptidase may partly be associated with the conversion of a latent form of type IV procollagenase to an active form or the secretion of the collagenases from tumor cells.     

Enhanced mitochondrial degradation of yeast cytochrome c with amphipathic structures

The dispensable N-terminus of iso-1-cytochrome c (iso-1) in the yeast Saccharomyces cerevisiae was replaced by 11 different amphipathic structures. Rapid degradation of the corresponding iso-1 occurred, with the degree of degradation increasing with the amphipathic moments; and this amphipathic-dependent degradation was designated ADD. ADD occurred with the holo-forms in the mitochondria but not as the apo-forms in the cytosol. The extreme mutant type degraded with a half-life of approximately 12 min, whereas the normal iso-1 was stable over hours. ADD was influenced by the ⁺/^– state and by numerous chromosomal genes. Most importantly, ADD appeared to be specifically suppressed to various extents by deletions of any of the YME1, AFG3, or RCA1 genes encoding membrane-associated mitochondrial proteases, probably because the amphipathic structures caused a stronger association with the mitochondrial inner membrane and its associated proteases. The use of ADD assisted in the differentiation of substrates of different mitochondrial degradation pathways.     

In the absence of major histocompatibility complex class II molecules,invariant chain is translocated to late endocytic compartments by autophagy

It has been suggested that the cytoplasmic amino-terminal tail of invariant chain (Ii) contains a sorting signal that directs trafficking of the major histocompatibility complex (MHC) class II: Ii oligomeric complex to endocytic compartments. This model is based, in part, on the observation that in the absence of MHC class II molecules, Ii is detectable in lysosomal structures, a phenotype that is dependent on an intact NH₂ terminus. However, the route by which Ii gains access to endosomal compartments in the absence of class II molecules remains uncertain. Here we report a mechanism that localizes Ii in lysosomal compartments independently of class II. We show that murine Ii can be detected by immunofluorescence within late endocytic compartments of stably transfected Ltk^? mouse fibroblasts. Immunochemical studies indicate that degradation of Ii in these cells is sensitive to the lysosomotropic agent ammonium chloride, yet the majority of Ii that undergoes this apparent lysosomal degradation is sensitive to the enzyme endoglycosidase H. This finding suggests that Ii may reach the lysosomal compartment by a route that bypasses the Golgi complex. Consistent with this possibility, we found that in contrast to Ii which is complexed to class II molecules, transport of free Ii to lysosomes is prevented by 3-methyladenine, an inhibitor of the autophagic pathway of protein degradation, a process which involves direct transport from the endoplasmic reticulum to lysosomes. These data suggest the route of transport that leads to endosomal localization of Ii in the absence of class II is distinct from that taken when expressed with class II. This forces a re-evaluation of the concept that the cytosolic tail of Ii contains a dominant Golgi-to-endosomal sorting signal.