The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in de...The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn's ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thin- ner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn's ileitis and UC may enablethe luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.展开更多
Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guine...Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.展开更多
目的探讨Hath1基因在不同病变组织中的表达,分析其在增生性息肉(HP)和无蒂锯齿状腺瘤/息肉(SSA/P)鉴别诊断中的意义。方法选择2015年4月—2019年12月于成都三六三医院接受结肠镜检查的患者,对其影像资料进行回顾分析。共筛选出35例HP、6...目的探讨Hath1基因在不同病变组织中的表达,分析其在增生性息肉(HP)和无蒂锯齿状腺瘤/息肉(SSA/P)鉴别诊断中的意义。方法选择2015年4月—2019年12月于成都三六三医院接受结肠镜检查的患者,对其影像资料进行回顾分析。共筛选出35例HP、63例SSA/P、3例SSA/P伴异型增生、5例传统锯齿状腺瘤(TSA)、10例管状腺瘤(TA)患者纳入本次研究,并选取15例正常结肠为对照组。利用免疫组化法检测Hath1在不同组织中的表达情况并进行比较。结果在正常组织中,Hath1染色见于间质性炎症细胞、隐窝细胞和上皮细胞的细胞核,染色强度一致。在HP组织中,Hath1染色见于所有的微泡和杯状细胞的隐窝内的细胞核,且强度与对照组相当,并且Hath1在HP黏膜脱垂的扭曲隐窝中的核染色强度也保持一致。而在SSA/P组织中,56例(91.8%)隐窝细胞核Hath1染色非常微弱或缺失,5例(8.2%)隐窝细胞核Hath1染色阳性的组织均来自左侧(直肠3例,乙状结肠2例)。在不同病灶定位(右侧结肠vs左侧结肠)(χ^(2)=31.452,P<0.01)或疾病类型(HP vs SSA/P)(χ^(2)=53.157,P<0.01)中Hath1染色阳性率的差异具有统计学意义(P<0.01)。此外,在伴有细胞学异常增生的SSA/P组织中,Hath1在发育不良的上皮细胞质中的表达呈弥漫性阳性着染。在TSA组织中,Hath1表达呈混合模式,同时有局灶性的表达缺失和强阳性核染色。在TA组织中,Hath1的表达为大部分的强阳性的核染色,同时伴有部分斑片状阴性表达。结论在HP和SSA/P组织中Hath1基因的表达强度对鉴别诊断具有较高的特异性和敏感性,有望辅助单纯形态学难以区分病例的确诊,值得深入研究。展开更多
Objective To study effects of Adenovirus -mediated Hath1 expression in guinea pig cochlea at one month after exposure to intensive noise. Methods Normal hearing guinea pigs, weighing 250-300g, received exposure to 200...Objective To study effects of Adenovirus -mediated Hath1 expression in guinea pig cochlea at one month after exposure to intensive noise. Methods Normal hearing guinea pigs, weighing 250-300g, received exposure to 200 rounds of impulse noise at 170 dB sound pressure level (SPL). The virus vector was inoculated into the left cochlea 1 month after noise exposure. Animals were tested using ABR and prepared for morphological examinations includeing immunocytochemistry and SEM 4 weeks after vector inoculation. Results The adenovirus mediated report gene expressed in the damaged area. There were no significant differences between treated and control animal in ABR threshold and morphologic changes. No new hair cells appeared in the Hath1 treated animals. Conclusion Forced hath1 over-expression in the cochlea 1 month after noise exposure does not lead to appearance of new hair cells.展开更多
基金Supported by The Robert Bosch Foundation Stuttgart Germany and the Emmy Noether program (Wehkamp J) of the Deutsche Forschungsgemeinschaft (DFG)
文摘The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn's ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thin- ner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn's ileitis and UC may enablethe luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.
基金National NaturalScience Foundation grants No.30730040 and No.30628030.
文摘Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.
文摘目的探讨Hath1基因在不同病变组织中的表达,分析其在增生性息肉(HP)和无蒂锯齿状腺瘤/息肉(SSA/P)鉴别诊断中的意义。方法选择2015年4月—2019年12月于成都三六三医院接受结肠镜检查的患者,对其影像资料进行回顾分析。共筛选出35例HP、63例SSA/P、3例SSA/P伴异型增生、5例传统锯齿状腺瘤(TSA)、10例管状腺瘤(TA)患者纳入本次研究,并选取15例正常结肠为对照组。利用免疫组化法检测Hath1在不同组织中的表达情况并进行比较。结果在正常组织中,Hath1染色见于间质性炎症细胞、隐窝细胞和上皮细胞的细胞核,染色强度一致。在HP组织中,Hath1染色见于所有的微泡和杯状细胞的隐窝内的细胞核,且强度与对照组相当,并且Hath1在HP黏膜脱垂的扭曲隐窝中的核染色强度也保持一致。而在SSA/P组织中,56例(91.8%)隐窝细胞核Hath1染色非常微弱或缺失,5例(8.2%)隐窝细胞核Hath1染色阳性的组织均来自左侧(直肠3例,乙状结肠2例)。在不同病灶定位(右侧结肠vs左侧结肠)(χ^(2)=31.452,P<0.01)或疾病类型(HP vs SSA/P)(χ^(2)=53.157,P<0.01)中Hath1染色阳性率的差异具有统计学意义(P<0.01)。此外,在伴有细胞学异常增生的SSA/P组织中,Hath1在发育不良的上皮细胞质中的表达呈弥漫性阳性着染。在TSA组织中,Hath1表达呈混合模式,同时有局灶性的表达缺失和强阳性核染色。在TA组织中,Hath1的表达为大部分的强阳性的核染色,同时伴有部分斑片状阴性表达。结论在HP和SSA/P组织中Hath1基因的表达强度对鉴别诊断具有较高的特异性和敏感性,有望辅助单纯形态学难以区分病例的确诊,值得深入研究。
基金supported by a Natural ScienceFoundation of China (NSFC) grant (# 30571017) to SMYJoint Research Fund for Overseas Chinese Young Scholars by NSFC (# 30628030) to DH and SMYNIH grant R01 DC 004696 from the NIDCD to DH
文摘Objective To study effects of Adenovirus -mediated Hath1 expression in guinea pig cochlea at one month after exposure to intensive noise. Methods Normal hearing guinea pigs, weighing 250-300g, received exposure to 200 rounds of impulse noise at 170 dB sound pressure level (SPL). The virus vector was inoculated into the left cochlea 1 month after noise exposure. Animals were tested using ABR and prepared for morphological examinations includeing immunocytochemistry and SEM 4 weeks after vector inoculation. Results The adenovirus mediated report gene expressed in the damaged area. There were no significant differences between treated and control animal in ABR threshold and morphologic changes. No new hair cells appeared in the Hath1 treated animals. Conclusion Forced hath1 over-expression in the cochlea 1 month after noise exposure does not lead to appearance of new hair cells.
