Omicron Subvariants, Including BA.4 and BA.5, Substantially Preserve T Cell Epitopes of Ancestral SARS-CoV-2

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Effects of Calcium Channel Blockers on Sodium-Free Contracture in Atrial Muscle of the Rabbit

Effects of organic and inorganic Ca-channel blockers on Na-Ca exchange system were investigated in the rabbit atrial muscle. Atrial muscle strips were perfused with Kr-free Tyrode solution in order to depress the sodium pump activity. Removal of external sodium(sodium being replaced by Tris) induced a contracture which reached a maximum after 1 min and effects of Ca-channel blockers on the magnitude of contracture were analysed. The results obtained were as follows: 1. In the concentrations of 30 pM, 100 pM and 300 ,uM Mn2 + increased the magnitude of Na-removal contracture, but decreased it in the concentration above 2 ,uM. Verapamil(IO-6 M) pretreatment did not alter the effect of Mn2+ on sodium-removal contracture. 2. La3+, as Mn2+, increased the magnitude of contracture in the concentrations of 30-300 pM, and decreased the contracture in higher concentrations(> 1 mM) more prominently than Mn2+ did. 3. 0-600 also increased the contracture in the concentrations of 5 x 10-8 M, 10-7 M and 5 x 10-7 M but had no effect in higher concentratlonsfl Orf - 10-5 M), On the other hand diltiazem had no dffect on the contracture in a wide range of concentrations (up to 10-4 M). From the above results, it is concluded that Mn2+, La3+ and 0600 in lower concentrations stimulate the Na-Ca exchange system, whereas, Mn2+, La3+ and 0-600 in higher concentrations depress the exchange system and that Na-Ca exchange might be regulated by Ca-channel blockers and this regulation is sensitive to the concentration of Ca-channel blockers

A Synonymous Genetic Alteration of LMX1B in a Family with Nail-Patella Syndrome

The gene responsible for nail-patella syndrome, LMX1B, has recently been identified on chromosome 9q. Here we present a patient with nail-patella syndrome and an autosomal dominant pattern of inheritance. A 17-year-old girl visited our clinic for the evaluation and treatment of proteinuria. She had dystrophic nails, palpable iliac horns, and hypoplastic patellae. Electron microscopy of a renal biopsy showed irregular thickening of the glomerular basement membrane. A family history over three generations revealed five affected family members. Genetic analysis found a change of TCG to TCC, resulting in a synonymous alteration at codon 219 in exon 4 of the LMX1B gene in two affected family members. The same alteration was not detected in an unaffected family member. This is the first report of familial nail-patella syndrome associated with an LMX1B in Korea mutation, However, we can not completely rule out the possibility that the G-to-C change may be a single nucleotide polymorphism as this genetic mutation cause no alteration in amino acid sequence of LMX1B

In Vitro and in Vivo Phototoxicity on Gastric Mucosa Induced by Methylene Blue

BACKGROUND: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. METHODS: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm RESULTS: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P \u3c 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P \u3c 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. CONCLUSIONS: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period

Anti-inflammatory effect of essential oil extracted from Pinus densiflora (Sieb. et Zucc.) wood on RBL-2H3 cells

The aim of this study is to identify the active compounds of the essential oil extracted from the Pinus densiflora (Sieb. et Zucc.) wood using the hydrodistillation method and evaluate their anti-inflammatory activity. The chemical composition of the oil was identified by GC–MS analysis, and its anti-inflammatory activity was assessed by investigating its effect on the expression of interleukin-4 (IL-4), interleukin-13 (IL-13), and β-hexosaminidase in lipopolysaccharide (LPS)-stimulated RBL-2H3 cells. Treatment of the LPS-stimulated RBL-2H3 cells with the oil and its fractions downregulated the production of pro-inflammatory cytokines such as IL-4 and IL-13 and further attenuated the secretion of β-hexosaminidase out of the cells to a significant level. Among the five obtained fractions, fraction E exhibited the best anti-inflammatory activity, and its main constituent, longifolene, was considered as the active compound. Moreover, the inhibitory effect of longifolene on the expression levels of IL-4 and IL-13 and the β-hexosaminidase secretion was similar to that of the P. densiflora wood oil, indicating longifolene as the active constituent of the P. densiflora wood oil with immunosuppressive effects on inflammation

Cytoprotective effects of fermented oyster extracts against oxidative stress-induced DNA damage and apoptosis through activation of the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblasts

Osteoblast damage by oxidative stress has been recognized as a cause of bone-related disease, including osteoporosis. Recently, we reported that fermented Pacific oyster (Crassostrea gigas) extracts (FO) inhibited osteoclastogenesis and osteoporosis, while promoting osteogenesis. However, since the beneficial potential of FO on osteoblasts is not well known, in the present study, we investigated the cytoprotective effect of FO against oxidative stress in MC3T3-E1 osteoblasts. Our results demonstrated that FO inhibited hydrogen peroxide (H2O2)-induced DNA damage and cytotoxicity through the rescue of mitochondrial function by blocking abnormal ROS accumulation. FO also prevented apoptosis by suppressing loss of mitochondrial membrane potential and cytosolic release of cytochrome c, decreasing the rate of Bax/Bcl-2 expression and reducing the activity of caspase-9 and caspase-3 in H2O2-stimulated MC3T3-E1 osteoblasts, suggesting that FO protected MC3T3-E1 osteoblasts from the induction of caspase dependent- and mitochondria-mediated apoptosis by oxidative stress. In addition, FO markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression of heme oxygenase-1 (HO-1). However, inhibiting the expression of HO-1 by artificially blocking the expression of Nrf2 using siRNA significantly eliminated the protective effect of FO, indicating that FO activates the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblasts to protect against oxidative stress. Based on the present data, FO is thought to be useful as a potential therapeutic agent for the inhibition of oxidative stress in osteoblasts

Evaluation in 3 Months Duration of Neointimal Coverage After Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography The ENDEAVOR OCT Trial

ObjectivesWe performed this study to investigate the vascular response in early period after zotarolimus-eluting stent (ZES) (Endeavor Sprint, Medtronic CardioVascular, Minneapolis, Minnesota) implantation.BackgroundThe ZES has different characteristics, with biocompatible polymer and rapid drug-elution, compared with the first-generation drug-eluting stents (DES).MethodsThe ENDEAVOR OCT (Evaluation in 3 Months Duration of Neointimal Coverage after Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography) trial is a prospective, single-center study evaluating vascular healing patterns with optical coherence tomography (OCT) at 3 months after stent implantation. A total of 31 ZES in 30 patients underwent serial OCT at immediate post-intervention and 3 months. Neointimal growth and malapposition were analyzed at each stent strut of cross-sectional OCT images with 0.5-mm intervals.ResultsThe incidence of malapposition at post-intervention and 3 months was 6.0% and 0.2%, respectively. However, late acquired malapposition was not detected at 3 months. Of 31 stents, 27 stents (87.1%) were covered completely with neointima, but the remaining 4 stents had 2 (0.8%), 4 (0.9%), 4 (1.2%), and 6 (1.4%) uncovered struts. Overall mean percentage of covered stent struts was 99.9 ± 0.4%. This finding was consistent among groups with acute coronary syndrome and stable angina pectoris (99.9 ± 0.3% vs. 99.9 ± 0.4%, p = 0.92). Intracoronary thrombus was documented in 1 stent (3.2%) among 31 stents.ConclusionsMost of the stent struts were covered with neointima, and late acquired malapposition was not found at 3 months after ZES implantation. Therefore, the current study demonstrated that ZES might have a favorable in vivo vascular response at 3 months after stent implantation. (Evaluation of Zotarolimus Eluting Stent at 3 Months Using Optical Coherence Tomography [ENDEAVOR OCT]; NCT00815139

Cystamine induces AIF-mediated apoptosis through glutathione depletion

AbstractCystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting γ-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death