Heme Oxygenase-1 Gene (GT)n Polymorphism Linked to Deep White Matter Hyperintensities, Not Periventricular Hyperintensities.

BACKGROUND: Oxidative stress plays a principal role in the pathogenesis of white matter hyperintensities (WMHs). The induction of heme oxygenase-1 (HO-1) gene in the brain represents 1 of the pivotal mechanisms to counteract the noxious effects of reactive oxygen species, and the transcriptional modulation of HO-1 induction depends on the length of a GT-repeat (GT)n in the promoter region. We investigated whether the HO-1 gene (GT)n polymorphism is associated with the risk of WMHs. METHODS AND RESULTS: A total of 849 subjects from the memory clinic were consecutively enrolled, and the HO-1 (GT)n genotype was determined. WMHs were assessed with the Fazekas scale and further divided into periventricular WMHs and deep WMHs (DWMHs). Allelic HO-1 (GT)n polymorphisms were classified as short (≤24 (GT)n), median (25≤[GT]n<31), or long (31≤[GT]n). Multivariate logistic regression analysis was used to evaluate the effect of the HO-1 (GT)n variants on WMHs. The number of repetitions of the HO-1 gene (GT)n ranged from 15 to 39 with a bimodal distribution at lengths 23 and 30. The proportion of S/S genotypes was higher for moderate/severe DWMHs than none/mild DWMHs (22.22% versus 12.44%; P=0.001), but the association for periventricular WMHs was not statistically significant. Logistic regression suggested that the S/S genotype was significantly associated with moderate/severe DWMHs (S/S versus non-S/S: odds ratio, 2.001 [95% CI, 1.323-3.027]; P<0.001). The HO-1 gene (GT)n S/S genotype and aging synergistically contributed to the progression of DWMHs (relative excess risk attributable to interaction, 6.032 [95% CI, 0.149-11.915]). CONCLUSIONS: Short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from DWMHs, but not periventricular WMHs. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100045869.

High glucose levels accelerate atherosclerosis via NLRP3-IL/ MAPK/NF-κB-related inflammation pathways.

BACKGROUND: As a chronic inflammatory disease, diabetes mellitus (DM) contributes to the development of atherosclerosis (AS). However, how the NLRP3 inflammasome participates in diabetes-related AS remains unclear. Therefore, this study aimed to elucidate the mechanism through which NLRP3 uses high glucose (HG) levels to promote AS. METHODS: Serum and coronary artery tissues were collected from coronary artery disease (CAD) patients with and without DM, respectively. The expression of NLRP3 was detected, and the effects of this inflammasome on diabetes-associated AS were evaluated using streptozotocin (STZ)-induced diabetic apoE-/- mice injected with Adenovirus-mediated NLRP3 interference (Ad-NLRP3i). To elucidate the potential mechanism involved, ox-LDL-irritated human aortic smooth muscle cells were divided into the control, high-glucose, Si-NC, and Si-NLRP3 groups to observe the changes induced by downregulating NLRP3 expression. For up-regulating NLRP3, control and plasmid contained NLRP3 were used. TNF-α, IL-1ß, IL-6, IL-18, phosphorylated and total p38, JNK, p65, and IκBα expression levels were detected following the downregulation or upregulation of NLRP3 expression. RESULTS: Patients with comorbid CAD and DM showed higher serum levels and expression of NLRP3 in the coronary artery than those with only CAD. Moreover, mice in the Ad-NLRP3i group showed markedly smaller and more stable atherosclerotic lesions compared to those in other DM groups. These mice had decreased inflammatory cytokine production and improved glucose tolerance, which demonstrated the substantial effects of NLRP3 in the progression of diabetes-associated AS. Furthermore, using the siRNA or plasmid to downregulate or upregulate NLRP3 expression in vitro altered cytokines and the MAPK/NF-κB pathway. CONCLUSIONS: NLRP3 expression was significantly increased under hyperglycemia. Additionally, it accelerated AS by promoting inflammation via the IL/MAPK/NF-κB pathway.

The study of clinicopathologic features of cervical squamous carcinoma with invasive micropapillary like pattern and phenotype.

Invasive micropapillary carcinoma has been reported in the adenocarcinoma of many organs including cervix, and many studies have proved it has more invasive biological behavior. This study, for the first time, reports cervical squamous carcinoma with invasive micropapillary like pattern and phenotype (IMLPP) and further investigates its clinicopathologic features. Cervical squamous carcinoma with IMLPP was selected by histological characteristics and immunohistochemical staining. All patients' clinical information and pathological parameters were collected. Based on histological characteristics and immunohistochemical staining results, 24 cases, out of 104 cases of cervical squamous carcinoma, were identified as having invasive micropapillary like pattern. The staining of all 24 cases with EMA and MUC-1 showed the feature of "reverse polarity like". Meanwhile, patient age at diagnosis (P=0.011), maximum invasion depth (P=0.001), maximum diameter (P=0.015), lymphvascular space invasion (P<0.001), pelvic lymph node metastasis (P<0.001), metastasis (P=0.020), death (P=0.025) and FIGO stages (P=0.001) were related to the existence of IMLPP, independently of the proportion of IMLPP to the whole tumor in size. Univariate and multivariate disease-free survival analyses (follow-up time >12 months) showed significant statistical difference between cervical squamous carcinoma with or without IMLPP (P=0.016, P=0.043). Results from our study suggested that IMLPP may be associated with aggressive biological behavior in cervical squamous carcinoma. Therefore, pathologists should pay attention to the existence of it, no matter its proportion with relation to the whole tumor, and bring it to the attention of clinicians.

A Highly Sensitive Nonenzymatic Glucose Biosensor Based on the Regulatory Effect of Glucose on Electrochemical Behaviors of Colloidal Silver Nanoparticles on MoS2†.

A novel and highly sensitive nonenzymatic glucose biosensor was developed by nucleating colloidal silver nanoparticles (AgNPs) on MoS2. The facile fabrication method, high reproducibility (97.5%) and stability indicates a promising capability for large-scale manufacturing. Additionally, the excellent sensitivity (9044.6 µA mM-1 cm-2), low detection limit (0.03 µM), appropriate linear range of 0.1-1000 µM, and high selectivity suggests that this biosensor has a great potential to be applied for noninvasive glucose detection in human body fluids, such as sweat and saliva.

Imaging of the anterior segment in glaucoma.

Although constituting only about a quarter of all glaucoma, angle closure glaucoma causes a disproportionate amount of visual morbidity and is predicted to be responsible for almost half of bilateral blindness by 2020. Early detection and treatment of angle closure significantly improves visual prognosis. Identification of eyes at risk of angle closure currently relies on opportunistic case detection, often by gonioscopy. However, gonioscopy is a highly subjective technique and often leads to misdiagnosis and underdetection of angle closure. More recently, various imaging modalities that allow a more objective assessment of the anterior segment structures, including anterior segment optical coherence tomography and the scanning peripheral anterior chamber depth analyser, have come under close scrutiny for their potential in screening for angle closure. Their accuracy and repeatability, advantages and disadvantages as well as their ease of use are all important to consider whether they are intended for use in the clinical setting or if they are to be incorporated into mass screening programs. Furthermore, their place alongside gonioscopy and more established technologies such as ultrasound biomicroscopy must be considered. The aim of this paper is to review the anterior segment imaging technologies that are currently available.