Mal de Meleda with homozygous mutation p.G86R in SLURP‐1 Jia, Wei‐Xue; Zhang, Yuan‐Yuan; Wu, Ying‐Da ...
International journal of dermatology,
June 2020, 2020-Jun, 2020-06-00, 20200601, Letnik:
59, Številka:
6
Journal Article
Osteosarcomas (OS) is a kind of malignant bone tumor which occurs primarily in children and adolescents, and the clinical therapeutics remain disappointing. As a new programmed cell death, ...ferroptosis is characterized by iron dependent and intracellular oxidative accumulation, which provides a potential alternative intervene for the OS treatment. Baicalin, a major bioactive flavone derived from traditional Chinese medicine Scutellaria baicalensis, has been proved to have anti-tumor properties in OS. Whether ferroptosis participated in the baicalin mediated anti-OS activity is an interesting project.
To explore the pro-ferroptosis effect and mechanisms of baicalin in OS.
Pro-ferroptosis effect of baicalin on cell death, cell proliferation, iron accumulation, lipid peroxidation production was determined in MG63 and 143B cells. The levels of glutathione (GSH), oxidized (GSSG) glutathione and malondialdehyde (MDA) were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Glutathione peroxidase 4 (GPX4) and xCT were detected by western blot in baicalin-mediated ferroptosis regulation. In vivo, a xenograft mice model was adopted to explore the anticancer effect of baicalin.
In the present study, it was found that baicalin significantly suppress tumor cell growth in vitro and in vivo. By promoting the Fe accumulation, ROS formation, MDA production and suppressing the ratio of GSH/GSSG, baicalin was found to trigger ferroptosis in OS and ferroptosis inhibitor ferrostatin-1 (Fer-1) successfully reversed these suppressive effects, indicating that ferroptosis participated in the baicalin mediated anti-OS activity. Mechanistically, baicalin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced its stability via inducing ubiquitin degradation, which suppressed the Nrf2 downstream targets GPX4 and xCT expression, and led to stimulating ferroptosis.
Our findings for the first time indicated that baicalin exerted anti-OS activity through a novel Nrf2/xCT/GPX4-dependent ferroptosis regulatory axis, which hopefully provides a promising candidate for OS treatment.
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To explore the changes in oral flora in people with functional dyspepsia (FD). Unstimulated saliva was collected from 21 FD patients diagnosed according to the Rome IV criteria and from 12 healthy ...controls (HCs) for 16SrRNA sequencing. The pH of saliva samples and community periodontal index (CPI) were tested. The prevalence of small intestinal bacterial overgrowth (SIBO) was obtained by the methane-and hydrogen-based breath test. At the phylum level, FD patients had a higher relative abundance of Spirochaetes and a lower relative abundance of Fusobacteria, TM7 and Proteobacteria than HCs (p < 0.01). In the saliva, Kingella and Abiotrophia genus levels showed significant changes between the FD and HC groups (p < 0.01). Salivary species level marker Intermedia was significantly different between FD and HC groups (p < 0.01). The oral pH of FD patients was higher than that of HCs (p < 0.01). The mean CPI of the FD group was 1.52 and that of the HC group was 0.17 (p < 0.01). Moreover, 71.4% of the FD group was positive for SIBO. The oral flora of FD patients was different from that of HCs. Spirochaetes, Kingella, Abiotrophia, and Intermedia may be diagnostic indicators of FD.
Molybdenum disulfide is considered one of the most promising anodes for lithium-ion batteries due to its high specific capacity; however, it suffers from an unstable solid electrolyte interphase. ...Understanding its structural evolution and reaction mechanism upon charging/discharging is crucial for further improvements in battery performance. Herein, the interfacial processes of solid electrolyte interphase film formation and lithiation/delithiation on ultra-flat monolayer molybdenum disulfide are monitored by in situ atomic force microscopy. The live formation of ultra-thin and dense films can be induced by the use of fluoroethylene carbonate as an additive to effectively protect the anode electrodes. The evolution of the fluoroethylene carbonate-derived solid electrolyte interphase film upon cycling is quantitatively analysed. Furthermore, the formation of wrinkle-structure networks upon lithiation process is distinguished in detailed steps, and accordingly, structure-reactivity correlations are proposed. These quantitative results provide an in-depth understanding of the interfacial mechanism in molybdenum disulfide-based lithium-ion batteries.
Significance: The light dose in photodynamic therapy (PDT) has a considerable influence on its treatment effect, and irradiance uniformity is an issue of much concern for researchers. However, ...achieving intelligent and personalized dosimetry adjustments remains a challenge for current PDT instruments.
Aim: To meet the requirements of intelligent and personalized dosimetry adjustments for the light dose on an irregular surface, a new PDT device with its optimal control method is proposed.
Approach: This research introduces a new PDT device that includes a 3D scanner, a light-emitting diode (LED) array, and a computer. The 3D scanner is proposed to generate the point cloud of the lesion and the LED array light source, and obtain the relative position and rotation parameters between them. Then, an image segmentation algorithm is used to segment the lesion point cloud into several cluster regions. Last, the current of each LED unit is adjusted separately to achieve the expected irradiance on each cluster.
Results: Compared with the general light source, the optimized light source increases the effective irradiance area by 9% to 15% and improves its uniformity by ∼9 % on a human port-wine stain head model.
Conclusions: The device and its optimal method may be used for optimizing the light dosimetry to realize intelligent and personalized treatment.
Indoor dust often contains organic contaminants, which adversely impacts human health. In this study, the organic contaminants in the indoor dust from commercial offices and residential houses in ...Nanjing, China were extracted and their effects on human breast cancer cells (MCF-7) were investigated. Both dust extracts promoted proliferation of MCF-7 cells at ≤24 μg/100 μL, with cell viability being decreased with increasing dust concentrations. Based on LC50, house dust was less toxic than office dust. At 8 μg/100 μL, both extracts caused more MCF-7 cells into active cycling (G2/M + S) and increased intracellular Ca2+ influx, with house dust inducing stronger effects than office dust. Further, the expression of estrogen-responsive genes for TFF1 and EGR3 was enhanced by 3-9 and 4-9 folds, while the expression of cell cycle regulatory genes for cyclin D was enhanced by 2-5 folds. The results suggested that organic dust extract influenced cell viability, altered cell cycle, increased intracellular Ca2+ levels, and activated cell cycle regulatory and estrogen-responsive gene expressions, with house dust showing lower cytotoxicity but higher estrogenic potential on MCF-7 cells. The results indicate the importance of reducing organic contaminants in indoor dust to mitigate their adverse impacts on human health.
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•Effects of organic dust extract on human breast cancer cells (MCF-7) were examined.•Both extracts stimulated proliferation of MCF-7 cells at ≤24 μg/100 μL.•Extracts reduced cell viability, altered cell cycle and enhanced intracellular Ca2+.•Extracts increased expression of estrogen-responsive & cell cycle regulatory genes.•House dust induced lower toxicity but higher estrogenic potential on MCF-7 cells.
Microbial degradation is considered the most promising method for removing phthalate acid esters (PAEs) from polluted environments; however, a comprehensive genomic understanding of the entire PAE ...catabolic process is still lacking. In this study, the repertoire of PAE catabolism genes in the metabolically versatile bacterium Rhodococcus sp. 2G was examined using genomic, metabolic, and bioinformatic analyses. A total of 4930 coding genes were identified from the 5.6 Mb genome of the 2G strain, including 337 esterase/hydrolase genes and 48 transferase and decarboxylase genes that were involved in hydrolysing PAEs into phthalate acid (PA) and decarboxylating PA into benzoic acid (BA). One gene cluster (xyl) responsible for transforming BA into catechol and two catechol-catabolism gene clusters controlling the ortho (cat) and meta (xyl &mhp) cleavage pathways were also identified. The proposed PAE catabolism pathway and some key degradation genes were validated by intermediate-utilising tests and real-time quantitative polymerase chain reaction. Our results provide novel insight into the mechanisms of PAE biodegradation at the molecular level and useful information on gene resources for future studies.
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•The strain 2G could efficiently degrade a wide range of PAEs.•A repertoire of the whole PAEs-catabolism process was obtained.•An array of genes involved in PAEs catabolic pathway in the 2G genome were excavated.•Strain 2G has two gene clusters of ring cleavage pathways in catechol degradation.
In corneal epithelium, tight junctions play a vital role in its barrier function. Human cornea is highly susceptible to damage by dust. Continued daily exposure to dust has been associated with ...increased risks of corneal injury. Studies demonstrated that water extract of dust induced cytotoxicity in human corneal epithelial cells (HCECs); however, its effects on corneal epithelial barrier function are unknown. In this study, we determined the concentrations of heavy metals in water extracts of dust, with office dust having higher concentrations of heavy metals than housedust, and Cu and Zn being highest among metals for both dust. Changes in barrier function and its associated mechanism after exposing HCECs to water extracts of dust at 48 μg/100 μ L for 7 d were evaluated. Water extracts of both dust caused decrease of TEER value (39–73%), down-regulation of gene expression related to tight junction and mucin (0.2–0.8 fold), and loss of ZO-1 immunoreactivity from cellular borders, with office dust having greater potential than housedust to disrupt corneal epithelial barrier function. Our data implied the importance to reduce heavy metals in dust to reduce their adverse impacts on human eyes.
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•Human corneas are countinually exposed to dust on a daily basis.•First report on effects of dust water extract on corneal epithelial barrier function.•Extracts decreased TEER value, tight junction and mucin related gene expression.•More loss of ZO-1 immunoreactivity was found in water extract of office dust.•Need to evaluate impact of dust on corneal barrier function.
Water extract of office dust had more impact than housedust on disruption of tight junction in normal human corneal epithelial cells.
Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious, economically important viral disease in many countries. The E(rns) and E2 envelope ...glycoproteins are responsible for the binding to and entry into the host cell by CSFV. To date, only one cellular receptor, heparan sulfate (HS), has been identified as being involved in CSFV attachment. HS is also present on the surface of various cells that are nonpermissive to CSFV. Hence, there must be another receptor(s) that has been unidentified to date. In this study, we used a set of small interfering RNAs (siRNAs) against a number of porcine cell membrane protein genes to screen cellular proteins involved in CSFV infection. This approach resulted in the identification of several proteins, and of these, the laminin receptor (LamR) has been demonstrated to be a cellular receptor for several viruses. Confocal analysis showed that LamR is colocalized with CSFV virions on the membrane, and a coimmunoprecipitation assay indicated that LamR interacts with the CSFV E(rns) protein. In inhibition assays, anti-LamR antibodies, soluble laminin, or LamR protein significantly inhibited CSFV infection in a dose-dependent manner. Transduction of PK-15 cells with a recombinant lentivirus expressing LamR yielded higher viral titers. Moreover, an attachment assay demonstrated that LamR functions during virus attachment. We also demonstrate that LamR acts as an alternative attachment receptor, especially in SK6 cells. These results indicate that LamR is a cellular attachment receptor for CSFV.
Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), an economically important viral disease affecting the pig industry in many countries. To date, only heparan sulfate (HS) has been identified to be an attachment receptor for CSFV. Here, using RNA interference screening with small interfering RNAs (siRNAs) against a number of porcine membrane protein genes, we identified the laminin receptor (LamR) to be another attachment receptor. We demonstrate the involvement of LamR together with HS in virus attachment, and we elucidate the relationship between LamR and HS. LamR also serves as an attachment receptor for many viral pathogens, including dengue virus, a fatal human flavivirus. The study will help to enhance our understanding of the life cycle of flaviviruses and the development of antiviral strategies for flaviviruses.
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