Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.     

Waning antibody levels after COVID-19 vaccination with mRNA Comirnaty and inactivated CoronaVac vaccines in blood donors,Hong Kong,April 2020 to October 2021

The mRNA vaccine Comirnaty and the inactivated vaccine CoronaVac are both available in Hong Kong’s COVID-19 vaccination programme. We observed waning antibody levels in 850 fully vaccinated (at least 14 days passed after second dose) blood donors using ELISA and surrogate virus neutralisation test. The Comirnaty-vaccinated group’s (n = 593) antibody levels remained over the ELISA and sVNT positive cut-offs within the first 6 months. The CoronaVac-vaccinated group’s (n = 257) median antibody levels began to fall below the cut-offs 4 months after vaccination.     

An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21

In our efforts to identify new loci responsible for non-syndromic autosomal recessive forms of deafness, DFNB loci, we have pursued the analysis of large consanguineous affected families living in geographically isolated areas. Here, we report on the study of a Lebanese family comprising nine members presenting with a pre-lingual severe to profound sensorineural isolated form of deafness. Linkage analysis led to the characterization of a new locus, DFNB21, which was assigned to chromosome 11q23-25. Already mapped to this chromosomal region was TECTA. This gene encodes alpha-tectorin, a 2155 amino acid protein which is a component of the tectorial membrane. This gene recently has been shown to be responsible for a dominant form of deafness, DFNA8/12. Sequence analysis of the TECTA gene in the DFNB21- affected family revealed a G to A transition in the donor splice site (GT) of intron 9, predicted to lead to a truncated protein of 971 amino acids. This establishes that alpha-tectorin mutations can be responsible for both dominant and recessive forms of deafness. Comparison of the phenotype of the DFNB21 heterozygous carriers with that of DFNA8/12-affected individuals supports the hypothesis that the TECTA mutations which cause the dominant form of deafness have a dominant-negative effect. The present results provide genetic evidence for alpha-tectorin forming homo- or heteromeric structures.      

Allele-specific late replication and fragility of the most active common fragile site, FRA3B

FRA3B at 3p14.2 is the most active of the common fragile sites in the human genome and is expressed when cells are exposed to the DNA replication inhibitor, aphidicolin. Several lines of evidence suggest that fragile sites are regions of late replication. To elucidate the relationship between the timing of replication across the FRA3B region and its corresponding fragility, we labeled cells with 5-bromo-2'- deoxyuridine (BrdU) and adopted an immunofluorescent procedure to visualize late replicating DNA (BrdU-substituted DNA) in metaphase chromosomes. We also chose 21 markers along the FRA3B region and analyzed the timing of replication using BrdU-labeled DNA from different stages of the cell cycle sorted by flow cytometry. Our results show that there are two distinct alleles that replicate at different stages in the cell cycle and that breaks/gaps preferentially occurred on the chromosome 3 with the late replication allele. These results provide direct evidence that allele-specific late replication is involved in the fragility of the most active common fragile site, FRA3B.      

Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study.

OBJECTIVE: Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men and women. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was performed among 49 young to middle-aged men and women who participated in the Miami Community Health Study. All participants had measures of insulin resistance (euglycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting serum leptin levels, and several measures of adiposity. RESULTS: The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentrations in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M was also inversely related to percent body fat and to the 2-h insulin area under the curve (AUC). After covariate adjustment for sex, percent body fat, and AUC, leptin remained a significant correlate of M (P = 0.04). CONCLUSIONS: Cross-sectionally, leptin was significantly associated with insulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistance association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.     

左半结肠癌梗阻外科治疗

左半结肠癌梗阻是常见的急腹症,手术治疗方式有多种［１－３］,本文简要综述可切除的左半结肠癌梗阻外科治疗方式,着重介绍了支架技术临床应用情况．１左半结肠癌梗阻的手术治疗１．１盲肠造口术（ｃｅｃｏｓｔｏｍｙ）盲肠造口安全简单,可在局麻下进行,一般应用于急...     

超声促进4,4-二取代-2-苯基-2-噁唑啉-5-酮的水解

目的碱性水解4,4-二取代-2-苯基-2-     

生长抑素及其受体与肝癌

生长抑素(somatostatin,SS)是一种环状多肽类激素,在体内有两种形式,即SS-14和SS-28,均具有显著的生物学活性[1,2],它们对生长激素(GH)、胰岛素、促胃液素等多种内、外分泌激素具有强大的抑制作用,并参与调节大脑运动和识别功能[3].近年研究显示,SS具有抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡功能,其生物学效应是通过靶细胞上特异性的生长抑素受体(human somatostatin receptor,hSSR)介导的[4,5].     

醋氯芬酸缓释片的研制

目的研制醋氯芬酸缓释片,评价其体外释药性质及释放机制.方法采用不同的高分子材料,按照均匀设计得到不同的处方,制成亲水凝胶骨架片,测定其释放度,并用SAS统计软件进行分析.结果处方R324h释放达95%以上,具有很好的缓释作用,其释放机制符合HixonCrowell方程,为亲水凝胶溶蚀与药物扩散共同作用的结果.结论该制剂体外释药性质主要受HPMCK4M和Carbopol934p的量及压力的影响.