IFNγ在动脉粥样硬化形成中的作用

干扰素γ（IFNγ）又称免疫干扰素，其抗病毒活性较低，免疫调节和抗细胞增殖作用较强，是一种强的巨噬细胞、NK细胞、血管内皮细胞活化剂。IFNγ增强抗原提呈，活化T淋巴细胞，与多种致炎因子相互作用，促进粥样病变处炎症反应，加重病变进展。作为脂质代谢相关酶的调节因子，IFNγ诱导泡沫细胞形成，并活化内皮细胞促进动脉粥样硬化。但也有研究显示，它可影响一些脂质受体抑制泡沫细胞形成，并减少平滑肌细胞增殖而对动脉粥样硬化形成起保护作用。     

Inactivation by 6-hydroxydopamine of the cerebral factor(s) responsible for the inhibition of the autoxidation of norepinephrine in vitro

The effect of extracts from rat cerebral cortex was examined on the stability of norepinephrine-HC1 (NE) in 16 mM Na-phosphate buffer, pH 7.4, at 37 degrees C. The autoxidation products of NE were detected spectrophotometrically at 480 nm. Dialysed samples from a synaptosomal preparation and from the 100,000 g supernatant of a crude homogenate were tested. Aliquots from these preparations, in the range of 0.005-5.0 or 0.01-10.0 micrograms protein/ml, respectively, produced up to 80-85% inhibition of the autoxidation of 100 microM NE for a period of at least 3 h. Similar results were obtained with albumin and ovalbumin at 10- and 10(3)-times higher concentrations, respectively. After the preparations were exposed to 0.1-1.0 mg 6-hydroxydopamine-HC1/mg protein for 5 min at 25 degrees C followed by rapid dialysis, the maximal inhibitory effect was reduced to between 95% to less than 5% of control values. The percent inactivation by a given quantity of 6-hydroxydopamine (6-OHDA) was inversely related to the potency of the untreated sample. Additional observations are presented which suggest that the destruction of the antioxidant activity is caused by breakdown products of 6-OHDA reacting with nucleophilic sites of the preparation. Similar inactivating substances are expected to be formed from other autoxidizing catecholamines, although at a slower rate.     

CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Increased central adiposity is associated with pro-inflammatory immunoglobulin G N-glycans

Background

Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.

Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome

Metabolic syndrome is characterized by obesity, elevated blood pressure (BP), insulin resistance, and hypercholesterolemia. Recently an animal model of this disorder has been proposed in rats selectively bred based on their performance on a treadmill-running task. Accordingly, low capacity runner (LCR) rats exhibited all of the diagnostic criteria for metabolic syndrome, including elevated BP, as compared to their high capacity runner (HCR) counterparts [U. Wisløff, S.M. Najjar, O. Ellingsen, P.M. Haram, S. Swoap, Q. Al-Share, M. Fernstrom, K. Rezaei, S.J. Lee, L.G. Koch, S.L. Britton, Cardiovascular risk factors emerge after artificial selection for low aerobic capacity, Science 307 (2005) 418–420]. Previous studies have highlighted the importance of GABAergic neurotransmission in the medullary cardiovascular-regulatory areas in the central control of BP. Thus, we hypothesized a dysregulation in GABAergic transmission in the medullary cardiovascular-regulatory nuclei of LCR rats. To begin testing this hypothesis we carried out experiments examining expression of the GABA synthetic enzymes, GAD65 and GAD67, mRNAs in the two rat strains via radioactive in situ hybridization. Our results showed GAD65 and GAD67 mRNAs were widely expressed throughout the brainstem; quantification revealed increased GAD65 mRNA expression in LCR animals in the caudal nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (VLM) as compared to HCR rats. Conversely, no differences in the expression of GAD67 were detected in these regions. These data are consistent with the notion of altered GABAergic neurotransmission in the NTS and VLM in metabolic syndrome, and point to the importance of these regions in cardiovascular regulation.     

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

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磷脂酶C-γ1在人胚胎脊髓中的表达变化

为了了解磷脂酶C-γ1(PLC-γ1)的发育表达变化特点,本研究采用免疫组织化学方法检测不同发育时期的人胚胎脊髓中PLC-γ1的表达及变化。结果显示:PLC-γ1在人胚胎脊髓3周到7个月的整个发育过程中均有表达,在发育早期阳性反应可见于神经管内、外界膜,随着套层、边缘层的形成,神经上皮层、套层中均可见到PLC-γ1阳性反应物,且翼板阳性细胞较基板密集;套层阳性细胞在8、9周时达到高峰,随后开始逐渐减少。3个月时边缘层出现散在的阳性细胞,并随着脊髓的发育而逐渐增多。以上结果提示,PLC-γ1及其与PLC-γ1相关的细胞信号通路对人胚胎脊髓的发育可能发挥了重要的生物学作用。     

Benzodiazepines both enhance gamma-aminobutyrate responses and decrease calcium action potentials in guinea-pig myenteric neurones

The effect of two benzodiazepines, midazolam and diazepam, was studied in guinea-pig myenteric neurones, using intracellular recording techniques. Both these benzodiazepines (100-300 pM) potentiated the rapidly desensitizing, bicuculline-sensitive depolarization, induced by alpha-aminobutyrate ionophoresis. Concentrations of midazolam and diazepam higher than 100 nM depressed the gamma-aminobutyrate-induced depolarization. The potentiating effect of the benzodiazepines was reversibly abolished by Ro 15-1788 (1-100 nM) and by pentylenetetrazol (100 microM). A second effect of midazolam and diazepam (100-300 pM) was a reversible depression of the amplitude and duration of the directly evoked action potential in 29% of neurones, without affecting membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and was also seen in the presence of tetrodotoxin. In some but not all of these neurones, the amplitude and duration of the action potentials was reduced also by gamma-aminobutyrate (1-10 microM). Ro 15-1788 and pentylenetetrazol reversibly abolished the effect of benzodiazepines on the action potential, but not that of gamma-aminobutyrate. Thus, benzodiazepines have two effects on myenteric neurones. The first is an enhancement of the gamma-aminobutyrate response (activation of Cl conductance); the second is a depression of the calcium action potential, which appears to be independent of gamma-aminobutyrate.     

The nucleus basalis magnocellularis: The origin of a cholinergic projection to the neocortex of the rat

The cells of origin of a neocortical cholinergic afferent projection have been identified by anterograde and retrograde methods in the rat. Horseradish peroxidase injected into neocortex labelled large, acetylcholinesterase-rich neurons in the ventromedial extremity of the globus pallidus. This same group of neurons underwent retrograde degeneration following cortical ablations. The region in which cell depletion occurred also showed significant decreases in the activities of choline acetyltransferase and acetylcholinesterase. Discrete electrolytic and kainic acid lesions restricted to the medial part of the globus pallidus each resulted in significant depletions of neocortical choline acetyltransferase and acetylcholinesterase. Hemitransections caudal to this cell group did not result in such depletions. Taken together these observations suggest that the acetylcholinesterase-rich neurons lying in the ventromedial extremity of the globus pallidus, as mapped in this study, constitute the origin of a major subcortical cholinergic projection to the neocortex. The utility of acetylcholinesterase histochemistry in animals pretreated with di-isopropylphosphorofluoridate in identifying cholinergic neurons is discussed in the light of this example; specifically, it is proposed that high acetylcholinesterase activity 4–8 h after this pretreatment is a necessary, but not sufficient, criterion for the identification of cholinergic perikarya.The neurons in question appear to be homologous to the nucleus basalis of the substantia innominata of primates, and are thus termed ‘nucleus basalis magnocellularis’ in the rat. No evidence was obtained to support the hypothesis that nucleus of the diagonal band projects to neocortex. However, striking similarities in size and acetylcholinesterase activity were observed among the putative cholinergic perikarya of the nucleus basalis magnocellularis, the nucleus of the diagonal band, and the medial septal nucleus.Kainic acid lesions of the neocortex produced uniform and complete destruction of neuronal perikarya. These lesions decreased neocortical glutamic acid decar?ylase activity, suggesting that there are GABAergic perikarya in the neocortex. However, the same lesions did not affect neocortical choline acetyltransferase. This observation suggests that there are no cholinergic perikarya in the neocortex, a conclusion that is consistent with the absence of intensely acetylcholinesterase-reactive neurons in the neocortex.