维甲酸对A549细胞增殖和凋亡及Skp2、p27^kip1蛋白表达的影响

目的探讨维甲酸对A549细胞增殖和凋亡及相关基因表达的影响。方法MTT法观察ATRA对A549细胞增殖的抑制作用;流式细胞仪、AO/EB荧光双染法检测细胞凋亡;免疫细胞化学检测ATRA处理前后A549细胞Skp2、p27^kip1蛋白表达的情况。结果ATRA处理后①MTT法结果显示ATRA对A549细胞具有增殖抑制作用,在一定范围内呈时间-剂量依赖性。②AO/EB荧光双染色法观察到ATRA 25μmol/L作用A549细胞48h后,即可发现典型的凋亡形态学改变。③流式细胞仪结果出现凋亡峰,与对照组细胞相比,实验组细胞周期延长,主要表现为G0/G1期细胞比例增加,同时S期细胞比例减少。④免疫细胞化学结果显示,ATRA 25μmol/L处理细胞48h后,维甲酸处理组Skp2有明显下调,p27^kip1则明显上调。结论ATRA具有抑制肺腺癌A549细胞增殖,诱导细胞凋亡的作用,其机制可能与下调Skp2,上调p27^kip1蛋白的表达水平有关。     

D609 对Neuro-2a 脑神经瘤细胞增殖和细胞周期的影响

目的:探讨小分子化合物D609对脑神经瘤细胞Neuro-2a的生长抑制及诱导细胞周期阻滞的效应,并初步研究其机制。方法:采用CCK-8法检测D609对Neuro-2a细胞的生长抑制作用;利用流式细胞术(FACS)检测D609处理对细胞周期进程的影响;利用免疫印迹实验(Western blot)检测不同浓度的D609处理后,细胞裂解液中细胞周期蛋白抑制因子p27的表达水平。结果:CCK-8的实验结果显示,加入150μmol/L D609处理72小时后,细胞生长受到明显地抑制,且伴有剂量依赖效应;流式细胞术的结果表明,D609处理使细胞周期阻滞在G0/G1期;免疫印迹的结果表明药物处理提升了p27的表达,且随药物浓度升高其表达亦增强。结论:D609可以有效地抑制Neuro-2a细胞的生长;进一步研究表明药物处理可以提升p27的表达水平并可以诱导将细胞阻滞在G0/G1期。因此,此研究将为脑神经瘤的治疗提供借鉴。     

姜黄素联合西达本胺通过下调AKT磷酸化和上调p53表达调控SKM-1细胞增殖和凋亡

该文探讨了姜黄素联合西达本胺对SKM-1细胞增殖和凋亡的影响及其作用机制。体外培养SKM-1细胞,取对数生长期细胞用于后续实验。对照组予以常规培养,实验组分别用不同浓度(1、5、10、20、40 μmol/L)姜黄素、不同浓度(0.5、1、2、4、8 μmol/L)西达本胺和不同浓度(5、10 μmol/L)姜黄素联合不同浓度(0.5、1、2、4、8 μmol/L)西达本胺处理细胞,采用CCK-8法检测各组细胞增殖活性,CompuSyn软件计算联合指数(combination index,CI),流式细胞术检测各组细胞周期分布和凋亡情况,Western blot检测各组细胞CDK2、p16、Caspase-3、AKT、p-AKT、p53和γH2A.X的蛋白表达水平。结果显示,在检测浓度范围内,姜黄素和西达本胺以时间浓度依赖性的方式抑制SKM-1细胞的生长。联合使用时,5 μmol/L姜黄素与2 μmol/L西达本胺具有协同抑制细胞增殖的作用。流式细胞术结果显示,5 μmol/L姜黄素联合2 μmol/L西达本胺组的细胞周期明显阻滞于G_0/G_1期,细胞凋亡率显著高于对照组和单独用药组。Western blot结果显示,与对照组相比,联合用药组的CDK2蛋白表达水平和p-AKT/AKT比例显著下降,而p16、Caspase-3、p53和γH2A.X的蛋白表达水平显著增高。综上,姜黄素联合西达本胺可显著抑制SKM-1细胞增殖,阻滞细胞周期,并促进细胞凋亡,其机制可能与抑制AKT磷酸化和上调p53表达有关。     

JKA97诱导HepG2凋亡及其分子机制研究

目的:研究药物JKA97对人肝癌细胞HepG2增殖的抑制作用及其分子机制.方法:采用MTT法观察药物JKA97对细胞增殖的影响;倒置显微镜观察细胞形态变化;流式细胞术检测细胞凋亡;Western blot方法检测线粒体融合蛋白mfn2表达水平变化.结果:药物JKA97抑制人肝癌细胞HepG2细胞增殖,5、10、20 μmol/L作用组24 h抑制率分别为34.26%、43.08%、54.02%;药物JKA97诱导人肝癌细胞HepG2凋亡,10、20 μmol/L JKA97作用HepG2细胞24h,细胞凋亡率分别为22.9%、72.9%;线粒体融合蛋白mfn2表达水平显著降低.结论:药物JKA97对人肝癌细胞HepG2生长具有明显的增殖抑制作用,诱导细胞凋亡;线粒体融合蛋白mfn2表达水平降低可能是其重要的分子机制之一.     

丙戊酸钠抑制A549细胞生长

目的研究丙戊酸钠对肺癌A549细胞增殖和细胞周期的影响。方法MTT检测生长抑制,流式细胞仪检测细胞周期和凋亡,Western blot检测p21WAF1/CIP1蛋白表达。结果丙戊酸钠以剂量依赖性方式抑制A549细胞生长;丙戊酸钠上调G0/G1期比例,下调S期和G2/M期,不影响细胞凋亡;丙戊酸钠上调p21WAF1/CIP1蛋白表达。结论丙戊酸钠上调p21WAF1/CIP1表达,使细胞阻滞于G0/G1期,抑制A549细胞生长。     

FOXO3a过表达对内皮祖细胞周期相关蛋白的调控

目的:观察FOXO3a(forkhead box O3a)的活性改变对内皮祖细胞(endothelial progenitor cells,EPCs)增殖和细胞周期相关蛋白表达的影响。方法:将携带突变激活FOXO3a基因的腺病毒载体Ad-TM(triple mutant)-FOXO3a和阴性对照腺病毒载体Ad-GFP体外感染人脐血来源的EPCs。观察EPCs形态学改变,CCK-8分析转染后EPCs增殖情况,Western blot检测FOXO3a蛋白、细胞周期相关蛋白p27kip1以及CDK2的表达水平。结果:构建了的2种腺病毒相关载体被成功转染。形态学改变方面,Ad-TM-FOXO3a组EPCs细胞生长缓慢,集落不明显;Western blot和CCK-8结果显示,Ad-TM-FOXO3a转染组与阴性对照组相比,EPCs增殖被抑制,FOXO3a与p27kip1蛋白过表达,CDK2表达下调。结论:FOXO3a可能通过上调p27kip1蛋白表达,下调CDK2表达,以抑制EPCs增殖。     

褪黑素抑制人骨肉瘤U2细胞增殖及其机制

目的研究褪黑素对体外培养人骨肉瘤U2细胞增殖的影响,并对其可能机制进行研究。方法体外培养U2细胞,用不同浓度褪黑素加以干预,以CCK-8法检测褪黑素对U2细胞增殖的影响;对细胞进行Hoechst 33258染色,荧光显微镜下观察褪黑素对U2细胞凋亡的影响;以流式细胞术检测褪黑素对细胞凋亡及细胞周期的影响;通过实时荧光定量PCR及免疫印迹法检测U2细胞Fas基因表达情况。结果 1 CCK8法检测显示褪黑素对U2细胞增殖有抑制作用,作用时间越长,浓度越高,抑制作用越明显;2 Hoechst33258染色可见凋亡小体;3流式细胞检测显示褪黑素作用后早期凋亡的U2细胞增加,并使细胞周期阻滞在G2/M期;4实时荧光定量PCR及免疫印迹法显示褪黑素处理后U2细胞上调Fas蛋白表达。结论褪黑素对U2细胞的增殖有抑制作用,可诱导细胞发生凋亡,其机制可能与将细胞复制周期阻滞在G2/M期及上调Fas蛋白表达量有关。     

抑癌基因NPRL2对肾癌786-O细胞增殖和凋亡的影响

抑癌基因NPRL2(nitrogen permease regulator-like 2)在人类许多正常组织中均有明显的表达,而在人类多种肿瘤组织中的表达明显降低。该实验通过构建重组质粒pEGFP-N1-NPRL2并转染肾癌786-O细胞株,应用倒置荧光显微镜、RT-PCR和Western blot检测NPRL2基因的表达情况;MTT法检测786-O细胞增殖的情况;流式细胞仪分析细胞周期和细胞凋亡情况。结果显示:肾癌786-O细胞株转染重组质粒pEGFP-N1-NPRL2后,通过荧光显微镜可以观察到绿色荧光;RT-PCR和Western blot检测到NPRL2基因的转录和蛋白质表达水平明显增加(P<0.05);MTT法检测发现72 h时pEGFP-N1-NPRL2组、pEGFP-N1组和空白对照组的细胞D490值分别为0.654±0.030、1.528±0.022和1.572±0.036,pEGFP-N1-NPRL2组细胞的增殖较其他两组受到明显的抑制(P<0.05);流式细胞仪检测显示pEGFP-N1-NPRL2组、pEGFP-N1组和空白对照组的凋亡率分别为18.82%±0.40%、5.65%±0.12%和5.85%±0.07%,而处于G0/G1期的细胞比例分别为69.80%±1.40%、46.24%±1.30%和47.03%±0.45%,与其他两组相比,pEGFP-N1-NPRL2组的凋亡率显著增高而且G0/G1期细胞明显增多,表现出G0/G1期阻滞。提示抑癌基因NPRL2的转染可以抑制786-O细胞的增殖,并诱导其凋亡将细胞周期阻滞于G0/G1期。     

长链非编码RNA PVT1促进胃癌细胞增殖和迁移

该文主要探讨了长链非编码RNA PVT1(long non-coding PVT1,Lnc RNA PVT1)对胃癌细胞增殖和迁移能力的影响。荧光定量PCR检测人胃癌细胞HGC-27、MGC-803和胃黏膜细胞GES-1中长链非编码RNA PVT1的表达水平;采用过表达技术和RNAi干扰技术分别上调和下调胃癌细胞MGC-803和HGC-27中PVT1的水平,CCK-8实验检测胃癌细胞增殖能力;流式细胞术检测细胞周期;细胞划痕和Transwell实验检测胃癌细胞的迁移能力;Western blot和荧光定量PCR检测p21和E-cadherin蛋白的表达。结果显示,胃癌细胞中Lnc RNA PVT1的表达显著高于胃黏膜细胞(P0.01),过表达PVT1后,胃癌细胞MGC-803的增殖和迁移能力明显增强(P0.01),p21和Ecadherin蛋白的表达明显降低(P0.01);而下调胃癌细胞中PVT1的表达后,胃癌细胞HGC-27的增殖和迁移能力明显下降(P0.01);p21和E-cadherin蛋白的表达明显增加(P0.01)。以上结果表明,胃癌细胞中Lnc RNA PVT1的水平显著高于胃黏膜细胞,Lnc RNA PVT1可以促进胃癌细胞增殖和迁移,有可能是通过调控p21和E-cadherin的表达发挥上述功能。     

α-倒捻子素通过激活ROS/p38 MAPK/Bax级联反应诱导B淋巴瘤Ramos细胞凋亡的机制研究CSCD

本文以B淋巴瘤Ramos细胞为研究对象,探讨α-倒捻子素(α-mangostin,α-Ma)对B淋巴瘤的增殖抑制作用并初步阐释其分子机制。首先通过CCK-8法探究α-Ma对Ramos细胞的增殖抑制作用;再利用倒置显微镜成像法观察α-Ma对Ramos细胞形态的影响;随后利用DCFH-DA、JC-1、Annexin V-FITC/PI荧光染色和流式细胞术检测α-Ma对Ramos细胞活性氧水平、线粒体膜电位、凋亡的影响;并通过蛋白免疫印迹技术测定α-Ma作用Ramos后细胞凋亡相关蛋白及信号通路蛋白的表达情况。CCK-8分析结果显示,α-Ma以药物浓度依赖和时间依赖的方式抑制Ramos细胞增殖,其24 h和48 h的IC值分别为14.84μmol/L和8.087μmol/L;倒置显微镜成像法发现α-Ma能减少Ramos细胞数量并诱导细胞形态发生凋亡样改变;流式细胞术检测发现,α-Ma能增加Ramos细胞内活性氧水平、降低细胞线粒体膜电位,同时诱导细胞凋亡;蛋白免疫印迹结果显示,α-Ma下调caspase-3/9的表达,上调cleaved caspase-3/9、cleaved PARP、Bax、Bim和p-p38 MAPK的表达。综上所述,α-Ma对B淋巴瘤Ramos细胞具有增殖抑制作用,其可能机制是α-Ma活化ROS/p38 MAPK/Bax级联反应诱导B淋巴瘤细胞凋亡。     

Long non‐coding RNA DBH‐AS1 promotes cancer progression in diffuse large B‐cell lymphoma by targeting FN1 via RNA‐binding protein BUD13

Diffuse large B‐cell lymphoma (DLBC) is a subtype of lymphoma with the worst prognosis. Existing treatment methods are not effective enough due to its high occurrence of metastasis. Therefore, identification of effective therapeutic targets is becoming increasingly important. In this research, long non‐coding RNA dopamine β hydroxylase antisense RNA 1 (DBH‐AS1) was found to be upregulated in DLBC tissues and cells. Knockdown of DBH‐AS1 suppressed the proliferation, migration, and invasion of cancer cells. Afterwards, RNA‐binding protein BUD13 homolog (BUD13) was found to be upregulated in cancer tissues and cells while binding to DBH‐AS1. Fibronectin 1 (FN1) was the downstream messenger RNA (mRNA) of BUD13. FN1 was upregulated in DLBC and was positively correlated with DBH‐AS1. Further rescue assays proved that DBH‐AS1 mediated FN1 expression by recruiting BUD13. In the meantime, BUD13 stabilized FN1 mRNA to promote FN1 expression. In this way, DBH‐AS1/BUD13/FN1 axis was confirmed. A set of rescue assays proved that DBH‐AS1 regulated DLBC progression via BUD13 and FN1. The function and mechanism of DBH‐AS1 were investigated for the first time in DLBC. DBH‐AS1 might become a therapeutic target in lymphoma treatment in the future.     

康莱特联合顺铂对宫颈癌SiHa细胞增殖和凋亡的影响

目的:通过康莱特联合顺铂对宫颈癌SiHa细胞增殖和凋亡的影响,探讨其作用机制。方法:体外培养宫颈癌Siha细胞,分别将康莱特(浓度为1,2,4,6,8 mg/mL),顺铂(浓度梯度为1.5,3,6,9,12μg/mL),单独作用于宫颈癌SiHa细胞,加药24h、48h用噻唑蓝(MTT法)检测细胞增殖情况。用流式细胞术检测康莱特组和顺铂组细胞24h凋亡率,选取合适的药物浓度(康莱特6 mg/mL,顺铂3μg/mL),进行联合用药,加药24h、48h用MTT法检测细胞增殖情况,用流式细胞术检测24h细胞凋亡率。结果:①MTT法显示加药后两组的24h、48h,宫颈癌SiHa细胞的抑制率均高于对照组(P0.05),并且在一定程度上呈浓度和时间依赖性。②联合用药时,细胞的抑制率和凋亡率要显著高于单独用药(P0.01)。结论:康莱特、顺铂单独或联合作用均能抑制SiHa细胞的增殖,促进其凋亡,且康莱特联合顺铂的作用要显著高于单独用药,康莱特与化疗药物联合使用可提高肿瘤细胞对化疗药物的敏感性。     

重楼皂苷Ⅶ抑制肺癌H460细胞增殖和迁移能力研究

为研究重楼皂苷Ⅶ(polyphyllin Ⅶ)抑制人肺癌H460细胞增殖、迁移能力和诱导凋亡的作用和机制。本实验采用MTT法检测重楼皂苷Ⅶ处理后H460细胞生长抑制率,Hoechst 33258染色观察细胞形态,细胞集落形成实验考察细胞的增殖能力,划痕实验和Transwell小室实验研究H460细胞迁移和侵袭能力的改变,并通过western blot法检测在重楼皂苷Ⅶ处理前后细胞蛋白表达变化情况。结果发现,重楼皂苷Ⅶ可显著抑制H460细胞增殖,影响其集落形成,并使细胞形态发生变化,抑制细胞体外的迁移和侵袭能力,并可诱导凋亡的发生。重楼皂苷Ⅶ处理后,H460细胞中基质金属蛋白酶MMP-2和MMP-9显著降低,凋亡相关蛋白剪切型caspase-3、Bax表达增加,ICAD、Bcl-2表达降低,提示重楼皂苷Ⅶ体外可能通过调节基质金属蛋白酶抑制H460细胞迁移和侵袭,同时诱导凋亡的发生。     

Bud8p and Bud9p, proteins that may mark the sites for bipolar budding in yeast

The bipolar budding pattern of a/alpha Saccharomyces cerevisiae cells appears to depend on persistent spatial markers in the cell cortex at the two poles of the cell. Previous analysis of mutants with specific defects in bipolar budding identified BUD8 and BUD9 as potentially encoding components of the markers at the poles distal and proximal to the birth scar, respectively. Further genetic analysis reported here supports this hypothesis. Mutants deleted for BUD8 or BUD9 grow normally but bud exclusively from the proximal and distal poles, respectively, and the double-mutant phenotype suggests that the bipolar budding pathway has been totally disabled. Moreover, overexpression of these genes can cause either an increased bias for budding at the distal (BUD8) or proximal (BUD9) pole or a randomization of bud position, depending on the level of expression. The structures and localizations of Bud8p and Bud9p are also consistent with their postulated roles as cortical markers. Both proteins appear to be integral membrane proteins of the plasma membrane, and they have very similar overall structures, with long N-terminal domains that are both N- and O-glycosylated followed by a pair of putative transmembrane domains surrounding a short hydrophilic domain that is presumably cytoplasmic. The putative transmembrane and cytoplasmic domains of the two proteins are very similar in sequence. When Bud8p and Bud9p were localized by immunofluorescence and tagging with GFP, each protein was found predominantly in the expected location, with Bud8p at presumptive bud sites, bud tips, and the distal poles of daughter cells and Bud9p at the necks of large-budded cells and the proximal poles of daughter cells. Bud8p localized approximately normally in several mutants in which daughter cells are competent to form their first buds at the distal pole, but it was not detected in a bni1 mutant, in which such distal-pole budding is lost. Surprisingly, Bud8p localization to the presumptive bud site and bud tip also depends on actin but is independent of the septins.     

一种新型PPARr激动剂对人肾癌细胞增殖抑制的实验研究

目的：探讨新型过氧化物酶体增殖激活物受体(PPARr)激动剂DH9 对人肾癌细胞OS-RC-2 的增殖抑制作用。方法：予以不 同浓度的DH9 及罗格列酮作用OS-RC-2 细胞12 h、24 h和48 h,荧光素酶活性检测比较两种药物的PPARr激动效应;MTT 法 检测细胞增殖情况;流式细胞术观察细胞周期;AnnexinV-FITC/PI双染色流式细胞术测定细胞凋亡率;Western blot 检测细胞内 Bax 及Bcl-2等蛋白的变化。结果：不同浓度的DH9 与罗格列酮相比,对PPARr的激动效应DH9明显低于罗格列酮,增殖抑制 作用优于罗格列酮(P＜0.05),并呈现明显的浓度、时间依赖性;加入PPARr抑制剂GW9662 前后DH9 的增殖抑制作用差异无统 计学意义(P＞0.05);DH9 作用细胞48小时后,G0/G1 期细胞比例明显增加(P＜0.05),S期细胞明显减少(P＜0.05)。DH9可诱导细 胞凋亡,伴随Bcl-2 表达的减少以及Bax表达的增加。结论：OS-RC-2 细胞中,DH9 的增殖作用明显优于罗格列酮,且是通过 PPARr非依赖途径实现;DH9 能将OS-RC-2 细胞阻滞在G0/G1 期,并通过影响Bcl-2 和Bax 蛋白表达促进细胞凋亡。     

Genetic analysis of the bipolar pattern of bud site selection in the yeast Saccharomyces cerevisiae.

Previous analysis of the bipolar budding pattern of Saccharomyces cerevisiae has suggested that it depends on persistent positional signals that mark the region of the division site and the tip of the distal pole on a newborn daughter cell, as well as each previous division site on a mother cell. In an attempt to identify genes encoding components of these signals or proteins involved in positioning or responding to them, we identified 11 mutants with defects in bipolar but not in axial budding. Five mutants displaying a bipolar budding-specific randomization of budding pattern had mutations in four previously known genes (BUD2, BUD5, SPA2, and BNI1) and one novel gene (BUD6), respectively. As Bud2p and Bud5p are known to be required for both the axial and bipolar budding patterns, the alleles identified here probably encode proteins that have lost their ability to interact with the bipolar positional signals but have retained their ability to interact with the distinct positional signal used in axial budding. The function of Spa2p is not known, but previous work has shown that its intracellular localization is similar to that postulated for the bipolar positional signals. BNI1 was originally identified on the basis of genetic interaction with CDC12, which encodes one of the neck-filament-associated septin proteins, suggesting that these proteins may be involved in positioning the bipolar signals. One mutant with a heterogeneous budding pattern defines a second novel gene (BUD7). Two mutants budding almost exclusively from the proximal pole carry mutations in a fourth novel gene (BUD9). A bud8 bud9 double mutant also buds almost exclusively from the proximal pole, suggesting that Bud9p is involved in positioning the proximal pole signal rather than being itself a component of this signal.     

Laboratory confirmation of Buruli ulcer disease in Togo, 2007-2010

Background

Since the early 1990s more than 1,800 patients with lesions suspicious for Buruli ulcer disease (BUD) have been reported from Togo. However, less than five percent of these were laboratory confirmed. Since 2007, the Togolese National Buruli Ulcer Control Program has been supported by the German Leprosy and Tuberculosis Relief Association (DAHW). Collaboration with the Department for Infectious Diseases and Tropical Medicine (DITM), University Hospital, Munich, Germany, allowed IS2404 PCR analysis of diagnostic samples from patients with suspected BUD during a study period of three years.

Methodology/Principal Findings

The DAHW integrated active BUD case finding in the existing network of TB/Leprosy Controllers and organized regular training and outreach activities to identify BUD cases at community level. Clinically suspected cases were referred to health facilities for diagnosis and treatment. Microscopy was carried out locally, external quality assurance (EQA) at DITM. Diagnostic samples from 202 patients with suspected BUD were shipped to DITM, 109 BUD patients (54%) were confirmed by PCR, 43 (29.9%) by microscopy. All patients originated from Maritime Region. EQA for microscopy resulted in 62% concordant results.

Conclusions/Significance

This study presents a retrospective analysis of the first cohort of clinically suspected BUD cases from Togo subjected to systematic laboratory analysis over a period of three years and confirms the prevalence of BUD in Maritime Region. Intensified training in the field of case finding and sample collection increased the PCR case confirmation rate from initially less than 50% to 70%. With a PCR case confirmation rate of 54% for the entire study period the WHO standards (case confirmation rate ≥50%) have been met. EQA for microscopy suggests the need for intensified supervision and training. In January 2011 the National Hygiene Institute, Lomé, has assumed the role of a National Reference Laboratory for PCR confirmation and microscopy.     

Effects of TGF-beta and glucocorticoids on map kinase phosphorylation, IL-6/IL-11 secretion and cell proliferation in primary cultures of human lung fibroblasts

Transforming growth factor-beta1 (TGF-beta1) is crucially involved in the fibrotic events characterizing interstitial lung diseases (ILDs), as well as in the airway remodeling process typical of asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts (HLFs), the effects of TGF-beta1 on mitogen-activated protein kinase (MAPK) phosphorylation, cell proliferation, and production of interleukins 6 (IL-6) and 11 (IL-11), in the presence or absence of a pretreatment with budesonide (BUD). MAPK phosphorylation was detected by Western blotting, cell viability and proliferation were evaluated using Trypan blue staining and [(3)H]-thymidine incorporation assay, respectively, and the release of IL-6 and IL-11 into cell culture supernatants was assessed by ELISA. TGF-beta1 (10 ng/ml) significantly stimulated MAPK phosphorylation (P < 0.01), and also enhanced cell proliferation as well as the secretion of both IL-6 and IL-11, which reached the highest increases at the 72nd h of cell exposure to this growth factor. All such effects were prevented by BUD (10(-8) M) and, with the exception of IL-6 release, also by a mixture of MAPK inhibitors. Therefore, our findings suggest that the fibrotic action exerted by TGF-beta1 in the lung is mediated at least in part by MAPK activation and by an increased synthesis of the profibrogenic cytokines IL-6 and IL-11; all these effects appear to be prevented by corticosteroids via inhibition of MAPK phosphorylation.     

Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo,Ghana and Togo

Background

The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guérin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD.

Methodology

The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors.

Principal Findings

After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions.

Conclusions

In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD.