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#36485005   2022/12/09 To Up

Polystyrene microplastic particles induce autophagic cell death in BEAS-2B human bronchial epithelial cells.

The detection of high levels of microplastics in indoor and outdoor air has increased concerns regarding its toxic effects on the respiratory system. They are not easily degradable and can be deposited deep in the lungs. Although several studies have reported inhalation toxicities of microplastics, they are still controversial due to a lack of evidence. Herein, we evaluated the inhalation toxicities of three differently charged polystyrene microplastics (PS-MPs), the most abundant microplastics in the air. Cytotoxicity and ROS generation were evaluated using WST-1 and DCF-DA assays, respectively. To evaluate the toxic effects on the lung, inflammatory responses were analyzed after repeated exposure to the PS-MPs through intratracheal instillation. To explore the mechanism of toxicity, autophagy and ER stress-associated proteins were analyzed. Only the positively charged PS-MPs (NH -PS-MPs) showed cytotoxicity and increased ROS generation in BEAS-2B cells. Similarly, only NH -PS-MPs significantly increased the expression and secretion of the pro-inflammatory cytokine IL-β in the animal experiments. The expression of ER stress proteins indicated that NH -PS-MPs increased ER stress via PERK-EIF2α and ATF4-CHOP pathways. Moreover, accumulation of NH -PS-MPs in lysosomes and deformity of the nucleus were observed in BEAS-2B cells with autophagy induction. Taken together, our results demonstrated that NH -PS-MPs induced autophagic cell death in bronchial epithelial cells, leading to inflammatory responses in the lungs. These results suggest that repeated inhalation of microplastics can result in inflammatory responses in the lung through cellular damage of lung epithelial cells, and that inhalation microplastics should be monitored to reduce inhalation health risks.
Mi Seon Jeon, Jun Woo Kim, Yu Bin Han, Mi Ho Jeong, Ha Ryong Kim, Hyung Sik Kim, Yong Joo Park, Kyu Hyuck Chung

2268 related Products with: Polystyrene microplastic particles induce autophagic cell death in BEAS-2B human bronchial epithelial cells.

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#36484997   2022/12/09 To Up

An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4.

Activity-based protein profiling (ABPP) is a versatile strategy for identifying and characterizing functional protein sites and compounds for therapeutic development. However, the vast majority of ABPP methods for covalent drug discovery target highly nucleophilic amino acids such as cysteine or lysine. Here, we report a methionine-directed ABPP platform using Redox-Activated Chemical Tagging (ReACT), which leverages a biomimetic oxidative ligation strategy for selective methionine modification. Application of ReACT to oncoprotein cyclin-dependent kinase 4 (CDK4) as a representative high-value drug target identified three new ligandable methionine sites. We then synthesized a methionine-targeting covalent ligand library bearing a diverse array of heterocyclic, heteroatom, and stereochemically rich substituents. ABPP screening of this focused library identified 1oxF11 as a covalent modifier of CDK4 at an allosteric M169 site. This compound inhibited kinase activity in a dose-dependent manner on purified protein and in breast cancer cells. Further investigation of 1oxF11 found prominent cation-π and H-bonding interactions stabilizing the binding of this fragment at the M169 site. Quantitative mass-spectrometry studies validated 1oxF11 ligation of CDK4 in breast cancer cell lysates. Further biochemical analyses revealed cross-talk between M169 oxidation and T172 phosphorylation, where M169 oxidation prevented phosphorylation of the activating T172 site on CDK4 and blocked cell cycle progression. By identifying a new mechanism for allosteric methionine redox regulation on CDK4 and developing a unique modality for its therapeutic intervention, this work showcases a generalizable platform that provides a starting point for engaging in broader chemoproteomics and protein ligand discovery efforts to find and target previously undruggable methionine sites.
Angel Gonzalez-Valero, Audrey G Reeves, Annika C S Page, Patrick J Moon, Edward Miller, Katia Coulonval, Steven W M Crossley, Xiao Xie, Dan He, Patricia Z Musacchio, Alec H Christian, Jeffrey M McKenna, Richard A Lewis, Eric Fang, Dustin Dovala, Yipin Lu, Lynn M McGregor, Markus Schirle, John A Tallarico, Pierre P Roger, F Dean Toste, Christopher J Chang

2591 related Products with: An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4.

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#36484982   2022/12/09 To Up

Stomatin-like Protein-2 Promotes Aggregation, Colonization and Migration of Endometriotic Cells.

Endometriosis is a chronic gynecological disease in women of childbearing age, which leads to infertility with risk of endometrial and ovarian cancer. The pathogenesis of endometriosis is poorly understood, and cure/treatment for it is not available, except for symptomatic treatment. The recurrence rate of endometriosis is high. SLP-2 is an inner mitochondrial membrane protein whose participation has been explained in cases of endometrial stromal cell growth, differentiation and migration, but its role in endometriosis is yet to be understood. Previous studies have found altered expression of stomatin-like protein 2 (SLP-2) in the serum of endometriotic patients. Therefore, we have studied the possible role of SLP-2 in the development of endometriosis. We found the ubiquitous and high expression of SLP-2 in the endometriotic tissue of both human endometriosis patients and rat endometriosis model. SLP-2 is seen in the glandular epithelial cells and stromal cells in the eutopic/normal or non-endometriosis group endometrium from human subjects. Finding high expression levels of SLP-2 in endometriotic tissue and ovarian cystic cells derived from endometriosis patients, we explored the possible role of SLP-2 in the cell aggregation, colonization, migration, and invasion in the human endometriotic cells associated with the progression of the endometriosis. Transient silencing of SLP-2 by its siRNA hinders endometriotic cells, aggregation, migration, and invasion into the extracellular matrix, which confirms SLP-2 involvement in endometriotic disease onset and progression. This study unravels the ubiquitous expression of SLP-2 in the human ectopic endometrial tissue and its role in the endometriotic cell migration, colonization, aggregation, and invasion leading to endometriosis progression.
Suparna Kumari, Pushplata Sankhwar, Rupal Tripathi, Ajay K Kawale, Satish Gupta, Rajesh Kumar Jha

1664 related Products with: Stomatin-like Protein-2 Promotes Aggregation, Colonization and Migration of Endometriotic Cells.

25UG250ul20000 U250ul1000 TESTS/0.65ml200ml25ml 5 x 200ul/Unit250ul25ml100ug Lyophilized

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#36484971   2022/12/09 To Up

Exploring the potential anti-Alzheimer disease mechanisms of Alpiniae Oxyphyliae Fructus by network pharmacology study and molecular docking.

Alpiniae Oxyphyliae Fructus (AOF) (yizhi) is a frequently medicated Chinese herb for Alzheimer disease (AD) treatment. The present study investigated the components and potential mechanisms of AOF through network pharmacology analysis and molecular docking. The results showed that AOF contains at least 20 active ingredients and involves 184 target genes. A total of 301 AD-related genes were obtained from the DisGeNET, GeneCards, GEO, OMIM, and Alzheimer Disease: Genes databases. A total of 41 key targets were identified from the topology analysis of the AOF-AD target network. These key targets are involved in 105 signal pathways, such as the PI3K-Akt, HIF-1, and MAPK pathways, and can regulate gene transcription, cell death, cell proliferation, drug response, and protein phosphorylation. AOF's active ingredients, Chrysin, Isocyperol, Izalpinin, Linolenic acid, CHEMBL489541, Oxyphyllenone A, Oxyphyllenone B, and Oxyphyllol C, show high affinity to targets, including PPARG, ESR1, and AKT1. These findings provide a new basis for AOF application and anti-AD study.
Rong-Rong Zhen, Yan-Jie Qu, Li-Min Zhang, Chao Gu, Min-Rui Ding, Lei Chen, Xiao Peng, Bing Hu, Hong-Mei An

2935 related Products with: Exploring the potential anti-Alzheimer disease mechanisms of Alpiniae Oxyphyliae Fructus by network pharmacology study and molecular docking.

1 mL100ul 50 UG0.1ml (1mg/ml)1000 0.1 mg1 mg96 tests100.00 ul500 tests

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#36484959   2022/12/09 To Up

Identification of the Genetic Association Between Type-2-Diabetes and Pancreatic Cancer.

Type-2-diabetes (T2D) and pancreatic cancer (PC) are both common diseases globally. Although T2D is reported as the adverse factor for predicting PC prognosis, its pathophysiology and relation with PC remain unknown. This study focused on exploring differentially expressed genes (DEGs) as well as their functional roles in T2D and PC, aiming to reveal the underlying association between the T2D and PC. To identify DEGs in T2D and PC, this study analyzed four microarray datasets obtained from Gene Expression Omnibus (GEO) database. Then, this work carried out enrichment as well as protein-protein interaction (PPI) network analysis for exploring DEGs-enriched functions and pathway. Besides, expression of hub genes was explored. TISIDB database was adopted to analyze the correlations among key gene and immune characteristics. Finally, the key gene expression was confirmed in vitro. DEGs were first screened from gene expression profiles of T2D and PC datasets, respectively. Then 135 common genes were identified in these four datasets. Based on functional analysis, common DEGs were mostly related to hormone secretion and metabolism pathways. Four hub genes were up-regulated, among which, MAFB was the most significant potential biomarker for PC. MAFB expression was strongly correlated with chemokines, chemokine receptors and immunomodulators. Finally, RT-qPCR was conducted to demonstrate the MAFB expression in T2D and PC. This study identified 15 hub genes with significant effects on the association of T2D with PC, and MAFB gene might be a biomarker for PC and had potential treatment value for PC.
Yaling Liang, Wei Chen, Yun Tang, Meijuan Chen

2542 related Products with: Identification of the Genetic Association Between Type-2-Diabetes and Pancreatic Cancer.

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#36484925   2022/12/09 To Up

S100A6 Activates Kupffer Cells via the p-P38 and p-JNK Pathways to Induce Inflammation, Mononuclear/macrophage Infiltration Sterile Liver Injury in Mice.

Noninfectious liver injury, including the effects of chemical material, drugs and diet, is a major cause of liver diseases worldwide. In chemical and drugs-induced liver injury, innate inflammatory responses are mediated by extracellular danger signals. The S100 protein can act as danger signals, which can promote the migration and chemotaxis of immune cells, promote the release of various inflammatory cytokines, and regulate the body's inflammatory and immune responses. However, the role of S100A6 in inflammatory response in chemical and drugs-induced sterile liver injury remains unclear. We constructed the model of sterile liver injury induced by carbon tetrachloride (CCl)/Paracetamol (APAP) and performed RNA sequencing (RNA-seq) on the liver tissues after injury (days 2 and 5). We analyzed inflammatory protein secretion in the liver tissue supernatant by enzyme-linked immunosorbent assay (ELISA), determined the inflammation response by bioinformatic analysis during sterile liver injury, and assessed mononuclear/macrophage infiltration by immunohistochemistry and flow cytometry. Immunohistochemistry was used to analyze the location of S100A6. We conducted inflammatory factor expression analysis and molecular mechanistic studies in Kupffer cells (KCs) induced by S100A6 using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), ELISA, and western blot in vitro experiments. We performed chemokine CCL2 expression analysis and molecular mechanism studies using the same method. We used a Transwell assay to show the infiltration of mononuclear/macrophage. We here observed that aggravated inflammatory response was shown in CCl and APAP-administrated mice, as evidenced by enhanced production of inflammatory cytokines (TNF-α, IL-1β), and elevated mononuclear/macrophage infiltration and activation of immunity. The expression of S100A6 was significantly increased on day 2 after sterile liver injury, which is primarily produced by injured liver cells. Mechanistic studies established that S100A6 activates Kupffer cells (KCs) via the p-P38, p-JNK and P65 pathways to induce inflammation in vitro. Furthermore, TNF-α can stimulate liver cells via the p-P38 and p-JNK pathways to produce CCL2 and promote the infiltration of mononuclear/macrophage. In summary, we showed that S100A6 plays an important role in regulating inflammation, thus influencing sterile liver injury. Our findings provide novel evidence that S100A6 can as a danger signal that contributes to pro-inflammatory activation through p-P38 and p-JNK pathways in CCl and APAP-induced sterile liver injury in mice. In addition, the inflammatory factor TNF-α induces a large amount of CCL2 production in normal liver cells surrounding the injured area through a paracrine action, which is chemotactic for blood mononuclear/macrophage infiltration.
He Tong, Li Wang, Kefan Zhang, Jing Shi, Yongshuai Wu, Yulong Bao, Changshan Wang

1848 related Products with: S100A6 Activates Kupffer Cells via the p-P38 and p-JNK Pathways to Induce Inflammation, Mononuclear/macrophage Infiltration Sterile Liver Injury in Mice.

10 ug1 mg400 ug8 Sample Kit100 ug/vial1.00 flask

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#36484920   2022/12/09 To Up

Bloodletting Acupuncture at Jing-Well Points Alleviates Myocardial Injury in Acute Altitude Hypoxic Rats by Activating HIF-1α/BNIP3 Signaling-Mediated Mitochondrial Autophagy and Decreasing Oxidative Stress.

To explore the protective effect and possible mechanisms of bloodletting acupuncture at Jing-well points (BAJP) pre-treatment on acute hypobaric hypoxia (AHH)-induced myocardium injury rat.
Chao Wang, Meng-Xin Li, Yun-di Li, Yong-Ping Li

2347 related Products with: Bloodletting Acupuncture at Jing-Well Points Alleviates Myocardial Injury in Acute Altitude Hypoxic Rats by Activating HIF-1α/BNIP3 Signaling-Mediated Mitochondrial Autophagy and Decreasing Oxidative Stress.

100 1 Set96 wells (1 kit)100 μg1 kit(96 Wells)96 wells (1 kit)96 wells (1 kit)96 wells (1 kit)96 wells (1 kit)100 μg96 wells (1 kit)20 µl (10 mM)

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#36484913   2022/12/09 To Up

Abundance, distribution, and expression of nematicidal crystal protein genes in Bacillus thuringiensis strains from diverse habitats.

Bacillus thuringiensis (Bt) is a Gram-positive bacterium that accumulates pesticidal proteins (Cry and Cyt) in parasporal crystals. Proteins from the Cry5, App6 (formerly Cry6), Cry12, Cry13, Cry14, Cry21, and Xpp55 (formerly Cry55) families have been identified as toxic to nematodes. In this study, a total of 846 Bt strains belonging to four collections were analyzed to determine the diversity and distribution of the Bt Cry nematicidal protein genes. We analyzed their presence by PCR, and positives were confirmed by sequencing. As a result, 164 Bt isolates (20%) contained at least one gene coding for nematicidal Cry proteins. The cry5 and cry21 genes were enriched in collection 1 and were often found together in the same strain. Differently, in collection 4, obtained from similar habitats but after 10 years, cry14 was the gene most frequently found. In collection 2, cry5 and app6 were the most abundant genes, and collection 3 had a low incidence of any of these genes. The results point to high variability in the frequencies of the studied genes depending on the timing, geographical origins, and sources. The occurrence of cry1A, cry2, and cry3 genes was also analyzed and showed that the nematicidal Cry protein genes were frequently accompanied by cry1A + cry2. The expression of the genes was assessed by mass spectrometry showing that only 14% of the positive strains produced nematicidal proteins. To our knowledge, this is the first comprehensive screening that examines the presence and expression of genes from the seven known Bt Cry nematicidal families.
Yolanda Bel, Miguel Andrés-Antón, Baltasar Escriche

1689 related Products with: Abundance, distribution, and expression of nematicidal crystal protein genes in Bacillus thuringiensis strains from diverse habitats.

100ug Lyophilized100.00 ug50 100ug Lyophilized0.1 mg1 Set1 Set501 Set1 Set100ug Lyophilized1 Set

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#36484868   2022/12/09 To Up

Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein-Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor.
K Abe, M Kitago, S Matsuda, M Shinoda, H Yagi, Y Abe, G Oshima, S Hori, Y Endo, T Yokose, E Miura, N Kubota, A Ueno, Y Masugi, H Ojima, M Sakamoto, Y Kitagawa

1395 related Products with: Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

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