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1.
肠道微生物群是指存在于人体消化道内的微生物组成的复杂群落。随着16S rRNA基因测序和宏基因组测序等高通量测序技术的发展,肠道微生物群已被证明与多种疾病息息相关。三大胰腺疾病与肠道微生物群密切相关,急性胰腺炎（acute pancreatitis,AP）、慢性胰腺炎（chronic pancreatitis,CP）和胰腺癌患者肠道微生物群的构成和丰度均与健康人群不同。反之,肠道微生物群的改变会减慢或加速胰腺疾病的发生发展。益生菌和抗菌药物的使用及粪菌移植等可减轻胰腺炎症反应,缓解胃肠道症状,影响胰腺癌化疗和免疫治疗的效果,因此可为胰腺疾病的诊疗提供新策略。本文总结了AP、CP和胰腺癌的肠道微生物群研究,阐述了疾病发生时肠道微生物群的变化、与胰腺相互作用的机制以及目前的主要研究技术,探讨了肠道微生物群在胰腺疾病诊疗中的研究进展。
相似文献2.
消化道微生态参与人体多种生理及病理过程,是消化领域的研究热点。消化道微生态可能与急慢性胰腺炎和胰腺癌等胰腺疾病关系密切,但学术界很少关注。慢性胰腺炎患者存在肠道菌群结构失衡,并易伴发小肠细菌过度生长。肠道菌群可能与自身免疫性胰腺炎等IgG4相关性疾病关系密切。急性胰腺炎患者存在肠道菌群结构变化,肠道屏障功能受损和细菌移位在急性胰腺炎疾病进展中起重要作用,但不同类型和疾病程度的急性胰腺炎患者肠道菌群结构和功能特征仍不清楚。牙周疾病和口腔微生态失衡会增加罹患胰腺癌的风险,但胰腺癌时肠道菌群的具体变化及作用仍不明确。本文就各类胰腺疾病背景下的消化道微生态研究现状及未来可能的研究方向进行阐述 相似文献
3.
目的:研究急性胰腺炎(AP)大鼠腺泡细胞凋亡,X连锁凋亡抑制蛋白(XIAP)的表达及其与疾病严重程度的关系。方法:通过胰胆管逆行注射不同浓度的牛黄胆酸钠,制备急性水肿型胰腺炎(AEP)和急性坏死性胰腺炎(ANP)大鼠模型,同时设假手术(SO)组为对照。收集各模型组3,6和12h标本,对胰腺组织进行病理学评分,并测定血清淀粉酶和腹水量;用TUNEL染色检测胰腺腺泡细胞的凋亡,分别RT-PCR和Western Blotting法测定大鼠胰腺组织XIAP mRNA及蛋白的表达。结果:成功建立了大鼠AP模型。同SO组相比,ANP和AEP组胰腺组织在各时间点均有不同程度的病理损害,血清淀粉酶也显著增高(P均<0.01)。且ANP组显著高于AEP组(P均<0.01)。造模成功3h后,各组大鼠胰腺腺泡细胞均出现少量凋亡,但ANP和AEP组凋亡显著多于SO组(P<0.05),ANP和AEP组间没有差别(P>0.05)。同SO组相比,ANP和AEP组在6h和12h时凋亡均增多(P<0.01),且AEP组显著高于ANP组(P<0.01)。造模成功3h后,各模型组XIAP mRNA表达没有差异(P>0.05);6h和12h时AEP组XIAP mRNA表达明显下降,而ANP组明显升高,两组间差异有显著性(P<0.01)。XIAP蛋白表达水平与mRNA表达水平相一致。结论:急性胰腺炎大鼠胰腺组织XIAP表达与腺泡细胞凋亡情况相反,且与疾病严重程度平行。XIAP可能负性调控AP大鼠胰腺腺泡细胞的凋亡。 相似文献
4.
Originally described as an interferon (IFN)-γ-inducing factor, interleukin (IL)-18 has been reported to be involved in Th1 and Th2 immune responses, as well as in activation of NK cells and macrophages. There is convincing evidence that IL-18 plays an important role in various pathologies (i.e. inflammatory diseases, cancer, chronic obstructive pulmonary disease, Crohn's disease and others). Recently, IL-18 has also been shown to execute specific effects in pancreatic diseases, including acute and chronic pancreatitis, as well as pancreatic cancer. The aim of this study was to give a profound review of recent data on the role of IL-18 and its potential as a therapeutic target in pancreatic diseases. The existing data on this topic are in part controversial and will be discussed in detail. Future studies should aim to confirm and clarify the role of IL-18 in pancreatic diseases and unravel their molecular mechanisms. 相似文献
5.
Yue T Partyka K Maupin KA Hurley M Andrews P Kaul K Moser AJ Zeh H Brand RE Haab BB 《Proteomics》2011,11(18):3665-3674
The current best serum marker for pancreatic cancer, CA 19-9, detects a carbohydrate antigen on multiple protein carriers. Better knowledge of the protein carriers of the CA 19-9 antigen in various disease states may lead to improved diagnostic tests. To identify proteins that carry the CA 19-9 antigen, we immunoprecipitated the CA 19-9 antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifications, we confirmed the presence of the CA 19-9 antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 antigen on the four proteins across various patient groups (pancreatic cancer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the carrier proteins of an important functional glycan and the rate at which the glycan is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein carriers of glycans and assess the diagnostic value of measuring glycans on individual proteins. 相似文献
6.
Giuseppina Simone 《Proteomics》2014,14(9):994-1000
Proteins play pivotal functions in cells; the study of these proteins and functions is the realm of proteomics. Less appreciated is that the proteins can be sugar coated and that glycosylation affects how the immune system recognizes the protein, as being friend or foe. Protein glycosylation and glycan‐protein interactions are involved in malignant processes, including those that underlie tumor, diabetes, and Alzheimer's disease. Some aspects of the glycome, including the role that simple glycans and their derivates have in the modulation of cellular behavior, have not yet been elucidated. Novel interdisciplinary technologies are needed to improve our understanding of those fields. Here, we describe the hierarchical levels of glycan structure and discuss the potential of microfluidics to gain an improved understanding of those mechanisms. 相似文献
7.
《Cell calcium》2018
In spite of significant scientific progress in recent years, acute pancreatitis (AP) is still a dangerous and in up to 5% of cases deadly disease with no specific cure. It is self-resolved in the majority of cases, but could result in chronic pancreatitis (CP) and increased risk of pancreatic cancer (PC). One of the early events in AP is premature activation of digestive pro-enzymes, including trypsinogen, inside pancreatic acinar cells (PACs) due to an excessive rise in the cytosolic Ca2+ concentration, which is the result of Ca2+ release from internal stores followed by Ca2+ entry through the store operated Ca2+ channels in the plasma membrane. The leading causes of AP are high alcohol intake and biliary disease with gallstones obstruction leading to bile reflux into the pancreatic duct. Recently attention in this area of research turned to another cause of AP – Asparaginase based drugs – which have been used quite successfully in treatments of childhood acute lymphoblastic leukaemia (ALL). Unfortunately, Asparaginase is implicated in triggering AP in 5–10% of cases as a side effect of the anti-cancer therapy. The main features of Asparaginase-elicited AP (AAP) were found to be remarkably similar to AP induced by alcohol metabolites and bile acids. Several potential therapeutic avenues in counteracting AAP have been suggested and could also be useful for dealing with AP induced by other causes. Another interesting development in this field includes recent research related to pancreatic stellate cells (PSCs) that are much less studied in their natural environment but nevertheless critically involved in AP, CP and PC. This review will attempt to evaluate developments, approaches and potential therapies for AP and discuss links to other relevant diseases. 相似文献
8.
Yong-Yu Li Xue-Jin Li Shuai Lv Kun Li Yan-Na Li Zhi-Rong Gao Jia-Yan Feng Chang-Jie Chen Claus Schaefer 《Cell stress & chaperones》2010,15(5):583-591
Acute pancreatitis (AP) is an inflammatory process in which cytokines and chemokines are involved. After onset, extrapancreatic stimuli can induce the expression of cytokines in pancreatic acinar cells, thereby amplifying this inflammatory loop. To further determine the role and mechanism of irritating agents in the pathogenesis of AP, rat pancreatic tissues were stimulated with ascitic fluid (APa) and serum (APs) from rats with AP or with lipopolysaccharide (LPS). In addition, the alteration of heat shock protein 60 (HSP60) expression was evaluated. Rat pancreas was removed and meticulously snipped to fragments. The snips were cultured for up to 48 h. During this period, the tissue viability as well as amylase and TNF-α levels in the supernatant and the HSP60 expression in the pancreatic tissue before and after stimulation by APa, APs, and LPS were assayed time-dependently. At different time-points during the culture, the viability and the amylase activity in the pancreatic tissue remained largely stable. After stimulation with APa, APs, or LPS for 1 h, the pancreatic tissues showed some damage, and this was followed by a sharp decrease in the viability accompanied by increased levels of amylase and TNF-α in the culture medium 2 or 4 h after stimulation (p < 0.05). In contrast, both the HSP60 mRNA and protein levels had a relatively high expression in the freshly prepared tissue fragments (0 h). As the culturing period was extended, the expression of HSP60 mRNA decreased only slightly; at the same time, the HSP60 protein levels decreased over a prolonged culture time, significantly so from 12 through 48 h (p < 0.05). After stimulation with APs, APa, or LPS, both the expression of HSP60 mRNA and protein in the tissue fragments increased slightly at 1 h and decreased significantly thereafter at 2 and 4 h (p < 0.05). APa, APs, or LPS induce injuries on isolated pancreatic tissues, accompanied by an altered HSP60 expression pattern in a time-dependent manner. 相似文献
9.
Koji Ueda Yu Fukase Toyomasa Katagiri Nobuhisa Ishikawa Shinji Irie Taka‐Aki Sato Hiroyuki Ito Haruhiko Nakayama Yohei Miyagi Eiju Tsuchiya Nobuoki Kohno Mieko Shiwa Yusuke Nakamura Professor Yataro Daigo 《Proteomics》2009,9(8):2182-2192
To screen for glycoproteins showing aberrant sialylation patterns in sera of cancer patients and apply such information for biomarker identification, we performed SELDI‐TOF MS analysis coupled with lectin‐coupled ProteinChip arrays (Jacalin or SNA) using sera obtained from lung cancer patients and control individuals. Our approach consisted of three processes (i) removal of 14 abundant proteins in serum, (ii) enrichment of glycoproteins with lectin‐coupled ProteinChip arrays, and (iii) SELDI‐TOF MS analysis with acidic glycoprotein‐compatible matrix. We identified 41 protein peaks showing significant differences (p<0.05) in the peak levels between the cancer and control groups using the Jacalin‐ and SNA‐ProteinChips. Among them, we identified loss of Neu5Ac (α2,6) Gal/GalNAc structure in apolipoprotein C‐III (apoC‐III) in cancer patients through subsequent MALDI‐QIT‐TOF MS/MS. Furthermore, subsequent validation experiments using an additional set of 60 lung adenocarcinoma patients and 30 normal controls demonstrated that there is a higher frequency of serum apoC‐III with loss of α2,6‐linkage Neu5Ac residues in lung cancer patients compared to controls. Our results have demonstrated that lectin‐coupled ProteinChip technology allows the high‐throughput and specific recognition of cancer‐associated aberrant glycosylations, and implied a possibility of its applicability to studies on other diseases. 相似文献
10.
Most MS-based glycomic and glycoproteomic analyses focus on identifying changes in terminal glyco-epitopes represented by sialylation and fucosylation at specific positions of the terminal N-acetyllactosamine units. Much less attention was accorded to the underlying linear or branched poly-N-acetyllactosamine extension from the N-glycan trimannosyl core other than a simple inference of its presence due to mass data and hence glycosyl compositional assignment. Using the EA.hy926 cell line derived from human umbilical vein endothelial cells (HUVEC), we have systematically investigated the MALDI- and ESI-MS-based methodologies for probing the structural details of endothelial polylactosaminoglycans at both MS and MS(2) levels in conjunction with the use of endo-β-galactosidase to identify branching motifs and initiation sites. We showed that the polylactosaminoglycan chains on the N-glycans of EA.hy926 were less sialylated and fucosylated but more extended and branched than those of human umbilical vein endothelial cells, thus demonstrating a fundamental glycomic difference. For EA.hy926 that was investigated in more details, its polylactosaminoglycan chains were shown to be not restricted to extending from a specific antenna including the biologically important 6-arm position. Finally, experimental conditions for glycopeptide enrichment by tomato lectin were further optimized, which led to identification of over 40 candidate endothelial membrane protein carriers of polylactosaminoglycans by proteomic analysis. 相似文献
11.
Some aberrant N‐glycosylations are being used as tumor markers, and glycoproteomics is expected to provide novel diagnosis markers and targets of drug developments. However, one has trouble in mass spectrometric glycoproteomics of membrane fraction because of lower intensity of glycopeptides in the existence of surfactants. Previously, we developed a glycopeptide enrichment method by acetone precipitation, and it was successfully applied to human serum glycoproteomics. In this study, we confirmed that this method is useful to remove the surfactants and applicable to membrane glycoproteomics. The glycoproteomic approach to the human fetal lung fibroblasts membrane fraction resulted in the identification of over 272 glycoforms on 63 sites of the 44 glycoproteins. According to the existing databases, the structural features on 41 sites are previously unreported. The most frequently occurring forms at N‐glycosylation site were high‐mannose type containing nine mannose residues (M9) and monosialo‐fucosylated biantennary oligosaccharides. Several unexpected N‐glycans, such as fucosylated complex‐type and fucosylated high‐mannose and/or fucosylated pauci‐mannose types were found in ER and lysosome proteins. Our method provides new insights into transport, biosynthesis, and degradation of glycoproteins. 相似文献
12.
The expression of heat-shock protein 60 (also known as chaperonin 60, Cpn60) in experimental acute pancreatitis (AP) is considered
to play an active role in the prevention of abnormal enzyme accumulation and activation in pancreatic acinar cells. However,
there are controversial results in the literature regarding the relationship between the abnormality of Cpn60 expression and
AP onset and development. The purpose of this study was to investigate the alternations of Cpn60 expression and the relationship
between the abnormal expression of Cpn60 and AP progression in rat severe acute pancreatitis (SAP) models. In this report,
we induced SAP in Sprague–Dawley (SD) rats by reverse injection of sodium deoxycholate into the pancreatic duct, and examined
the dynamic changes of Cpn60 expression in pancreatic tissues from different time points and at different levels with techniques
of real-time PCR, western blotting, and immunohistochemistry. At 1 h after SAP induction, the expression of Cpn60 mRNA in
the AP pancreatic tissues was higher than those in the sham-operation group and normal control group, but decreased sharply
as the time period was extended, and there was a significant difference between 1 h and 10 h after SAP induction (p < 0.05). In the AP process, Cpn60 protein expression showed transient elevation as well, and the increased protein expression
occurred predominantly in affected, but not totally destroyed, pancreatic acinar cells. As AP progressed, the pancreatic tissues
were seriously damaged, leading to a decreased overall Cpn60 protein expression. Our results show a complex pattern of Cpn60
expression in pancreatic tissues of SAP rats, and the causality between the damage of pancreatic tissues and the decrease
of Cpn60 level needs to be investigated further.
Xue-Li Li and Kun Li contributed equally to this work. 相似文献
13.
Anna Maria Ierardi Mario Petrillo Raffaella Capasso Federico Fontana Alessandro Bacuzzi Ejona Duka Domenico Laganà Gianpaolo Carrafiello 《Journal of medical case reports》2015,9(1)
Introduction
We report on the successful endovascular treatment of a ruptured splenic artery pseudoaneurysm. Our patient had acute pancreatitis superimposed on chronic calcific pancreatitis and chronic renal impairment. Contrast-enhanced ultrasonography was used to assess post-embolization results.Case presentation
Our patient was a 67-year-old white Caucasian man with recurrent pancreatitis. Computed tomography angiography showed a pancreatic pseudocyst with a ruptured pseudoaneurysm, which was successfully embolized using an endovascular percutaneous approach. At six months, persistent renal failure led to contrast-enhanced ultrasonography. This confirmed the absence of turbulent blood flow and extravasation of contrast medium in the pseudocyst.Conclusion
Our experience with this case leads us to support the role of interventional radiology as a first-line treatment tool. Contrast-enhanced ultrasonography can be used to follow-up embolization procedures in patients with impaired renal function. 相似文献14.
Serum amyloid P component (SAP) is a glycoprotein of interest due to its presence in amyloid plaque formations. As with most glycoproteins, SAP can possibly vary greatly in its isoforms, which can be an important factor toward understanding the role of SAP. Interestingly, previous characterizations suggest varying degrees of microheterogeneity, some of which are in conflict. In this work, we provide new information to clarify SAP's microheterogeneity profile using CIEF to carefully analyze pooled samples and by studying individual samples across populations with mass spectrometric immunoassay. With respect to CIEF, a single pI band was observed suggesting that human SAP does not have extensive heterogeneity concluded from gel IEF experiments in the past. Additionally, this is supported by a population study, which revealed an overwhelming degree of uniformity. Overall, this work corroborates the idea that SAP is relatively consistent across the population and with respect to microheterogeneity. 相似文献
15.
目的:探讨乌司他丁用于治疗不同类型急性胰腺炎的临床疗效和安全性。方法:收集2013年1月至2014年1月我院收治的急性胰腺炎患者84例,随机分为观察组与对照组,每组各42例,两组患者均给予常规治疗,对照组加用奥曲肽治疗,观察组在对照组的基础上加用乌司他丁治疗,观察和比较两组患者的临床疗效、治疗前后血清IL-6和TNF-α水平的变化及不良反应的发生情况。结果:观察组的总有效率为96.72%,显著高于对照组的85.71%;其中,两组急性水肿型胰腺炎的疗效相当(P0.05),但观察组出血坏死型胰腺炎的有效率显著高于对照组(P0.05)。治疗后,两组血清IL-6与TNF-α水平均较治疗前显著降低,并且观察组显著低于对照组(P0.05),水肿型胰腺炎患者血清IL-6及TNF-α水平显著低于出血坏死型胰腺炎患者,差异均具有统计学意义(P0.05)。两组均未发生肝肾功能损害,未见药物相关性不良反应。结论:乌司他丁用于辅助治疗急性胰腺炎能够明显下调炎症因子水平,临床疗效显著,对急性水肿型胰腺炎的疗效尤为显著,安全性好,值得推广应用。 相似文献
16.
目的：探讨磁共振多序列成像对鉴别胰头癌与胰头肿块型慢性胰腺炎的临床价值及意义。方法：对已确诊的16例胰头癌患者和5例胰头肿块型慢性胰腺炎患者的磁共振多序列成像MR进行回顾性分析。主要征象包括：①肿块信号及形态学特点;②胰管及胆管扩张情况;③动态增强的特征;④胰周及大血管受累情况;⑤邻近器官受累与淋巴结肿大情况。检查方法包括：平扫T1WI＋FST2WI＋FS,MRCP,3D—VIBE动态增强扫描。结果：1）肿块形态信号异常：胰头癌与胰头肿块型胰头慢性胰腺炎的信号有较多重叠,在TlwI上均表现为相对低信号,T2WI表现为不均匀稍高、相等或低信号。2）胰管与胆管的异常：胰头癌表现为胰管扩张至肿块处突然截断12例,胆总管突然截断10例,“双管征”10例。胰头肿块型慢性胰腺炎胰管扩张3例,2例为串珠样扩张,扩张的胰管可贯通病灶区,胆总管5例均扩张,远端呈短锥形狭窄3例,鼠尾样狭窄2例。3）3D—VIBE强化特征分析结果：随着时间的延长胰头癌强化程度和强化百分率较胰头肿块型慢性胰腺炎明显减低。4）胰周大血管受累情况：胰头癌肿块与血管分界不清者8例,部分包绕血管6例完全包绕血管6例;胰头肿块型慢性胰腺炎1例与血管分界不清,1例部分被包绕。5）邻近器官受累与淋巴结肿大情况：胰头癌有7例淋巴结肿大主要分布在胰周及腹主动脉旁,胰头肿块型慢性胰腺炎,未见明显肿大淋巴结,有四例肾周筋膜增厚,两例肾前筋膜增厚。结论：磁共振多序列成像的联合使用及征象分析,有助于鉴别胰头癌与胰头肿块型慢性胰腺炎。 相似文献
17.
Pavel Bouchal Monika Dvorakova Alexander Scherl Spiros D. Garbis Rudolf Nenutil Borivoj Vojtesek 《Proteomics》2013,13(7):1053-1058
Proteomics profiling of intact proteins based on MALDI‐TOF MS and derived platforms has been used in cancer biomarker discovery studies. This approach suffers from a number of limitations such as low resolution, low sensitivity, and that no knowledge is available on the identity of the respective proteins in the discovery mode. Nevertheless, it remains the most high‐throughput, untargeted mode of clinical proteomics studies to date. Here we compare key protein separation and MS techniques available for protein biomarker identification in this type of studies and define reasons of uncertainty in protein peak identity. As a result of critical data analysis, we consider 3D protein separation and identification workflows as optimal procedures. Subsequently, we present a new protocol based on 3D LC‐MS/MS with top‐down at high resolution that enabled the identification of HNRNP A2/B1 intact peptide as correlating with the estrogen receptor expression in breast cancer tissues. Additional development of this general concept toward next generation, top‐down based protein profiling at high resolution is discussed. 相似文献
18.
Prostate cancer is highly heterogeneous in nature; while the majority of cases are clinically insignificant, some cases are lethal. Currently, there are no reliable screening methods for aggressive prostate cancer. Since most established serum and urine biomarkers are glycoproteins secreted or leaked from the diseased tissue, the current study seeks to identify glycoprotein markers specific to aggressive prostate cancer using tissue specimens. With LC‐MS/MS glycoproteomic analysis, we identified 350 glycopeptides with 17 being altered in aggressive prostate cancer. ELISA assays were developed/purchased to evaluate four candidates, that is, cartilage oligomeric matrix protein (COMP), periostin, membrane primary amine oxidase (VAP‐1), and cathepsin L, in independent tissue sets. In agreement with the proteomic analysis, we found that COMP and periostin expressions were significantly increased in aggressive prostate tumors while VAP‐1 expression was significantly decreased in aggressive tumor. In addition, the expression of these proteins in prostate metastases also follows the same pattern observed in the proteomic analysis. This study provides a workflow for biomarker discovery, prioritization, and evaluation of aggressive prostate cancer markers using tissue specimens. Our data suggest that increase in COMP and periostin and decrease in VAP‐1 expression in the prostate may be associated with aggressive prostate cancer. 相似文献
19.
Xingwang Jia Jing Chen Shisheng Sun Weiming Yang Shuang Yang Punit Shah Naseruddin Hoti Bob Veltri Hui Zhang 《Proteomics》2016,16(23):2989-2996
Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. The blood prostate‐specific antigen test has facilitated early detection and intervention of prostate cancer. However, blood prostate‐specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. In the current study, we evaluated urine specimens from prostate cancer patients using LC‐MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N‐linked glycosite‐containing peptides and LC‐MS/MS. A total of 2923 unique glycosite‐containing peptides were identified. Glycoproteomic comparison on urine and tissues from aggressive and non‐aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 相似文献
20.