Relative importance of maternal and embryonic microsomal epoxide hydrolase in 7,12-dimethylbenz[a]anthracene-induced developmental toxicity

Microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of epoxide intermediates derived from drugs and environmental chemicals. The response of in vivo (embryo) and in vitro (embryo fibroblast) tests were analyzed using mEH-null and wild-type mice to determine the relative role of maternal and embryonic mEH in the developmental toxicity induced by 7,12-dimethylbenz[a]anthracene (DMBA). Embryos derived from DMBA-treated [50mg/kg, daily from gestational day (GD) 11 to GD 15] dams were analyzed. Although weight (P=0.0009) and crown-rump length (P=0.0003) of wild-type fetuses on GD 18 were significantly lower than those of mEH-null fetuses, respectively, no significant difference was found between mEH-null and heterozygous fetuses of mEH-null dams. Cell viability was decreased to 50% in wild-type mouse embryo fibroblasts (MEFs) treated with 3 microM DMBA, but no significant decrease was found in mEH-null MEFs. DMBA-3,4-diol produced a significant decrease in cell viability and suppressed the proliferation of wild-type MEFs at a 10-fold lower concentration than did DMBA. Although mEH protein was expressed in liver microsomes from wild-type embryos (GD 15), DMBA-3,4-diol was not detected among the DMBA metabolites. However, it was detected in the serum of wild-type pregnant mice treated with DMBA, but not in that of mEH-null mice. These results suggest that maternal mEH plays a major role in DMBA-induced developmental toxicity, and embryonic mEH is less involved in the toxicity.     

GD1a对基质金属蛋白酶-9在不同细胞类型中表达的调控作用

目的在不同的细胞类型中,检测神经节苷脂GD1a是否抑制基质金属蛋白酶-9(MMP-9)的表达。方法采用逆转录PCR法和酶谱法检测MMP-9及MMP-2的表达。结果在鼠黑色素瘤B16细胞中,神经节苷脂GD1a促进MMP-9的表达,而在小鼠肺癌Lewis细胞、人单核细胞THP-1及人子宫颈癌HeLa细胞中,神经节苷脂GD1a降低MMP-9的表达。在上述细胞中,神经节苷脂GD1a不影响基质金属蛋白酶MMP-2的表达;肿瘤坏死因子TNF-α在这几种细胞中均能促进MMP-9的表达,但对MMP-2无影响;在B16细胞中,GD1a通过胞窖膜介导信号传递,并且主要通过ERK促进MMP-9的表达,而在Lewis细胞中,GD1a不通过胞窖膜介导信号传递,但部分通过p38、ERK和JNK抑制MMP-9表达。结论在不同的细胞类型中,神经节苷脂GD1a能够激活不同的信号转导途径。     

An Investigation into the Stability of Sulfur Mustard and Soman in Perfluorooctylbromide

ABSTRACT

Perfluorooctylbromide (PFOB) was investigated as a potential stabilizer of sulfur mustard (HD) and soman (GD) because of its physical-chemical properties and its low toxicity. Separately, HD and GD solutions in PFOB were tested from ?70°C to 50°C by using nuclear magnetic resonance (NMR) and were found to be stable. When mixed with 10% (v/v) H₂O, the HD/PFOB sample decomposed (t_1/2 = 37 hours at 22°C), whereas the GD/PFOB sample remained unchanged for more than 24 hours. For additional identification before H₂O addition, the compounds were extracted from PFOB with acetonitrile and analyzed by using gas chromatography mass spectrometry (GCMS), and HD and GD were readily identified in their respective samples. We demonstrated by NMR and GCMS that PFOB solutions of HD and GD maintained their stability over a wide range of temperatures. We demonstrated by NMR that PFOB extended the stability of HD and GD when exposed to H₂O. These results prompt us to offer PFOB as a potential candidate for sample collection, preservation, and forensic analysis of HD and GD evidence and as a preservative vehicle for research on tissue exposed to chemical warfare agents.     

Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review

Background and objective

Numerous autoimmune diseases (AIDs) have been linked to chronic spontaneous urticaria (CSU). Here, we provide the first extensive and comprehensive evaluation of the prevalence of AIDs in patients with CSU and vice versa.

A rare case of systemic sclerosis complicated with multiple autoimmune diseases (Sjögren's syndrome,Graves' disease,and primary biliary cirrhosis)

Abstract

We report the case of a 54-year-old woman with systemic sclerosis and Sjögren's syndrome, followed by a simultaneous onset of Graves' disease and primary biliary cirrhosis. Eight years after the patient was diagnosed with systemic sclerosis and secondary Sjögren's syndrome, she complained of thirst and lower extremity muscle weakness. Initially, these symptoms were thought to be due to her original diseases, but laboratory data revealed thyroid dysfunction as well as liver dysfunction, and further tests confirmed the diagnoses of Graves' disease and primary biliary cirrhosis. The patient was treated with thiamazole and ursodeoxycholic acid. Following treatment, her symptoms were relieved, and laboratory data improved. Although a combination of these diseases is rare, it is important to keep in mind that various autoimmune diseases can occur simultaneously, and early detection and therapy are important.     

Transcranial magnetic stimulation (TMS) for geriatric depression

BackgroundThe prevalence of treatment-resistant geriatric depression (GD) highlights the need for treatments that preserve cognitive functions and recognize polypharmacy in elderly, yet effectively reduce symptom burden. Transcranial magnetic stimulation (TMS) is a proven intervention for treatment-resistant depression in younger adults but the efficacy of TMS to treat depressed older adults is still unclear. This review provides an updated view on the efficacy of TMS treatment for GD, discusses methodological differences between trials in TMS application, and explores avenues for optimization of TMS treatment in the context of the ageing brain.MethodsA systematic review was conducted to identify published literature on the antidepressant efficacy of TMS for GD. Databases PubMed, Embase, and PsycINFO were searched for English language articles in peer-reviewed journals in March 2021.ResultsSeven randomized controlled trials (RCTs) (total n = 260, active n = 148, control n = 112) and seven uncontrolled trials (total n = 160) were included. Overall, we found substantial variability in the clinical response, ranging from 6.7% to 54.3%.ConclusionsThe reviewed literature highlights large heterogeneity among studies both in terms of the employed TMS dosage and the observed clinical efficacy. This highlights the need for optimizing TMS dosage by recognizing the unique clinical features of GD. We showcase a set of novel approaches for the optimization of the TMS protocol for depression and discuss the possibility for a standardized TMS protocol tailored for the treatment of GD.     

Intracellular mediators of programmed cell death initiated at the cell surface receptor Fas

Abstract Apoptosis is a programmed cell death process, which plays a pivotal role in development, in tissue homeostasis and in several human diseases. Fas (CD95/Apo‐1) is a member of the “death receptors” family, a group of cell surface proteins that trigger apoptosis upon binding with their natural ligands. In the immune system, intracellular signal transduction triggered from Fas splits into two different pathways. The proteolytic pathway is mediated by a family of cysteine proteases, the caspases, responsible for the morphological changes occurring in the apoptotic process. To complete this death program, another series of events, involving a lipid pathway, is necessary. Upon Fas stimulation, a sequential activation of specific enzymes results in the accumulation of ceramides and GD3 ganglioside. GD3 directly induces mitochondrial damage and triggers the release of apoptogenic factors, allowing efficient execution of Fas‐mediated apoptosis.