Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes

1. Download : Download high-res image (143KB)
2. Download : Download full-size image

     

The Effects of Psychological Stress on Depression

Major depressive disorder is a serious mental disorder that profoundly affects an individual''s quality of life. Although the aetiologies underlying this disorder remain unclear, an increasing attention has been focused on the influence imposed by psychological stress over depression. Despite limited animal models of psychological stress, significant progress has been made as to be explicated in this review to elucidate the physiopathology underlying depression and to treat depressive symptoms. Therefore, we will review classical models along with new methods that will enrich our knowledge of this disorder.     

Maspin inhibits macrophage phagocytosis and enhances inflammatory cytokine production via activation of NF-κB signaling

Maspin (mammary serine protease inhibitor) is a non-inhibitory member of the serine protease inhibitor superfamily and a tumor suppressor in several cancers due to its ability to inhibit cell invasion, angiogenesis, and promote apoptosis. However, its immunomodulatory function remains largely unexplored. Thus, we explored the potential link between Maspin and macrophage function, first evaluating the regulatory effects of conditioned medium (CM) of a Maspin-overexpressing CHO cell strain on mouse peritoneal macrophage phagocytosis and cytokine secretion. Next, we used a transwell co-culture system and recombinant Maspin (rMaspin) to confirm the effects of Maspin on macrophages, and attempted to clarify the underlying mechanisms. We found that irrespective of CM, rMaspin or co-culture of Maspin-overexpressing cells with macrophages impaired macrophages phagocytosing Saccharomyces cerevisiae. Furthermore, q-RT-PCR or ELISA confirmed increased IL-1β, TNF-α, IFN-γ, IL-6, IL-12, IL-10, and M1 marker iNOS production in macrophages after Maspin stimulation, but TGF-β and M2 marker Arg-1 production were suppressed. Western blot showed activated NF-κB signaling in Maspin-stimulated macrophages; upregulated cytokines were lowered, and impaired phagocytosis recovered after blocking NF-κB signaling with PDTC. Thus, Maspin mildly inhibited phagocytic activity, but markedly enhanced inflammatory cytokine production and likely skewed macrophages towards M1 polarization, partially due to activation of NF-κB signaling. These results reveal a novel biological function of Maspin in modulating macrophage activity and may open a new avenue for Maspin-based tumor therapy.     

Inhibition of human natural killer cell functional activity by human aspartyl β-hydroxylase

Natural killer (NK) cells are a key component of the innate immune system and play pivotal roles as inflammatory regulators and in tumor surveillance. Human aspartyl β-hydroxylase (HAAH) is a plasma membrane and endoplasmic reticulum protein with hydroxylation activity, which is over-expressed in many malignant neoplasms and can be detected from the sera of tumor patients. HAAH is involved in regulating tumor cell infiltration and metastasis. Escaping from immune surveillance may help tumor cell infiltration and metastasis. However, the effects of HAAH on tumor immune surveillance have not yet been investigated carefully. The present study investigated the potential use of HAAH as an immune regulator of human NK cells. We assessed the effects of recombinant HAAH (r-HAAH) on primary human NK cell morphology, viability, cytotoxicity, apoptosis, receptors expression and cytokine/cytolytic proteins production. Our results demonstrated that r-HAAH negatively affects NK cell activity in a time and dose-dependent manner. It noticeably reduces the viability of the NK cells by increasing apoptosis and necrosis via caspase signaling pathways. Moreover, r-HAAH reduces the NK cell cytotoxicity by inhibiting surface expression of NKG2D, NKp44 and IFN-γ secretion. These findings suggest that one of the ways by which HAAH actively promotes tumor formation and proliferation is by inhibiting NK cell-surveillance activity.     

How active perception and attractor dynamics shape perceptual categorization: A computational model

We propose a computational model of perceptual categorization that fuses elements of grounded and sensorimotor theories of cognition with dynamic models of decision-making. We assume that category information consists in anticipated patterns of agent–environment interactions that can be elicited through overt or covert (simulated) eye movements, object manipulation, etc. This information is firstly encoded when category information is acquired, and then re-enacted during perceptual categorization. The perceptual categorization consists in a dynamic competition between attractors that encode the sensorimotor patterns typical of each category; action prediction success counts as “evidence” for a given category and contributes to falling into the corresponding attractor. The evidence accumulation process is guided by an active perception loop, and the active exploration of objects (e.g., visual exploration) aims at eliciting expected sensorimotor patterns that count as evidence for the object category. We present a computational model incorporating these elements and describing action prediction, active perception, and attractor dynamics as key elements of perceptual categorizations. We test the model in three simulated perceptual categorization tasks, and we discuss its relevance for grounded and sensorimotor theories of cognition.     

一种改良的人DNA微量快速检验技术

目的 探索一种以口腔粘膜脱落细胞为材料的安全、高效、低成本、敏感性高的人DNA微量快速检测方法。方法 采用从漱口液或棉签擦拭口腔粘膜获取脱落细胞,应用混合树脂（Chelex100）煮沸沉淀法提取DNA;用PCR分别对线粒体特异性DNA片断和基因组中的特定基因进行扩增检测。结果 通过对线粒体DNA中440 bp的非编码片段和染色体基因组中220 bp的乙醛脱氢酶DNA片段进行扩增,结果显示,从漱口液脱落细胞提取的DNA中可以稳定地扩增出上述两种DNA片断。结论 建立了一种改良的人口腔粘膜脱落细胞DNA微量快速检验技术。该法取样方便,DNA样品获取量较大,一次取样可同时进行多项线粒体和基因组标志DNA片段的快速PCR检测。     

Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy

IntroductionThe first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates.MethodPatients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study.ResultsThe study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT.ConclusionThe use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.     

Hinokitiol Inhibits Candida albicans Adherence to Oral Epithelial Cells

Candida spp. are an opportunistic pathogen causing serious local and systemic infections, especially in immuno-compromised hosts such as the elderly and HIV-positive patients. Hinokitiol C₁₀H₁₂O₂ (β-thujaplicin) is a component of the essential oils isolated from Cupressaceae and shows antibacterial activities for various bacteria. The aim of this study was to demonstrate the preventive effects of hinokitiol on the adherence of seven species of Candida to oral epithelial cells and to establish a safe and useful method for oral hygiene. A short-time treatment (30 min) with 0.25 mM hinokitiol showed 30–70% inhibition of adherence of Candida spp. to oral epithelial cells, inhibited about 11% biofilm formation, and did not inhibit the cell growth of Candida spp. Furthermore, short treatment with 0.25 mM hinokitiol was a safe method for oral hygiene against Candida infection because it did not inhibit the cell growth of commensal bacteria, such as oral streptococci existing in normal flora, or damage the epithelial cells. However, long-time treatment and a high concentration of hinokitiol demonstrated both the adherence inhibition of Candida and damage to commensal bacteria and epithelial cells. Our data suggest an appropriate procedure to apply hinokitiol that may be beneficial for the prevention of opportunistic pathogens such as Candida spp. in the oral cavity. The clinical and daily use of hinokitiol under an appropriate procedure may be a preventive and realistic therapy for Candida infection in immune-compromised hosts.