Inhibition of Suicidal Erythrocyte Death by Indirubin-3’-Monoxime

Background/Aims: Qing Dai is a prized traditional Chinese medicine whose major component, indirubin, and its derivative, indirubin-3’-monoxime (IDM), have inhibitory effects on the growth of many human tumor cells and pronounced anti-leukemic activities. However, the effects of IDM on mature human erythrocytes are unclear. This study aimed to evaluate the potential impact of IDM on erythrocytes and the mechanisms underlying that impact. Methods: Utilizing flow cytometry and confocal laser scanning microscopy, phosphatidylserine exposure at the cell surface was estimated by annexin V-fluorescein isothiocyanate (FITC). The relative cell size, expressed in arbitrary units, was evaluated by forward scatter in a flow cytometer. Fluo-3 fluorescence was used to bewrite changes in cytosolic Ca2+ activity, reactive oxygen species (ROS) formation was assessed by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence, and ceramide abundance was evaluated by FITC-conjugated specific antibodies. Results: The 24-h exposure of human erythrocytes to IDM (12 µM) significantly decreased the percentage of annexin V-binding erythrocytes and the intracellular calcium concentration ([Ca2+]i). IDM (3-12 µM) did not significantly modify the ceramide level or DCFH-DA fluorescence. Energy depletion (removal of glucose for 24 hours) significantly increased annexin V binding and Fluo-3 fluorescence and diminished forward scatter, and these effects were significantly mitigated by IDM (12 µM). Moreover, the Ca2+ ionophore ionomycin (1 µM, 60 min) and oxidative stress (30 min exposure to 0.05 mM tert-butyl hydroperoxide, t-BHP) similarly triggered eryptosis, which was also significantly suppressed by IDM. Conclusions: IDM is a novel inhibitor of suicidal erythrocyte death following ionomycin treatment, t-BHP treatment and energy depletion. Thus, IDM may counteract anemia and impairment of microcirculation, at least in part, by inhibition of Ca2+ entry into erythrocytes

ZDHHC11B is decreased in lung adenocarcinoma and inhibits tumorigenesis via regulating epithelial–mesenchymal transition

Abstract Purpose The role and mechanism of zinc finger DHHC protein 11B (ZDHHC11B) in lung adenocarcinoma (LUAD) remain unclear. We, thus, analyzed the expression pattern, biological function, and potential mechanism of ZDHHC11B in LUAD. Methods The expression level and prognostic value of ZDHHC11B were evaluated based on The Cancer Genome Atlas (TCGA) database and further confirmed in LUAD tissues and cells. The effect of ZDHHC11B on the malignant biological progression of LUAD was evaluated in vitro and in vivo. Gene set enrichment analysis (GSEA) and western blot were used to explore the molecular mechanisms of ZDHHC11B. Results In vitro, ZDHHC11B inhibited the proliferation, migration, and invasion of LUAD cells and induced the apoptosis of LUAD cells. In addition, ZDHHC11B inhibited the growth of tumors in nude mice. GSEA revealed that ZDHHC11B expression is positively correlated with epithelial–mesenchymal transition (EMT). Western blot analysis demonstrated that molecular markers of EMT were inhibited under ZDHHC11B overexpression conditions. Conclusions Our findings indicated that ZDHHC11B plays a significant role in inhibiting tumorigenesis via EMT. In addition, ZDHHC11B may be a candidate molecular target for LUAD treatment

Diseleno[2,3‑<i>b</i>:3′,2′‑<i>d</i>]selenophene and Diseleno[2,3‑<i>b</i>:3′,2′‑<i>d</i>] thiophene: Building Blocks for the Construction of [7]Helicenes

New building blocks, 2,5-di­(trimethylsilanyl)­diseleno­[2,3-<i>b</i>:3′,2′-<i>d</i>]­selenophene ((TMS)₂-<b>DSS</b>) and 2,5-di­(trimethylsilanyl)­diseleno­[2,3-<i>b</i>:3′,2′-<i>d</i>]­thiophene ((TMS)₂-<b>DST</b>), for helicenes were obtained from selenophene with total yields of 54 and 61%. From (TMS)₂-<b>DSS</b> and (TMS)₂-<b>DST</b>, selenophene-based hetero[7]­helicenes, 5,5′-di­(trimethylsilanyl)­benzo­[1,2-<i>b</i>:3,4-<i>b</i>′]­bis­(diseleno­[2,3-<i>b</i>:3′,2′-<i>d</i>]­thiophene) (<i>rac</i>-<b>1</b>), and 5,5′-di­(trimethylsilanyl)­benzo­[1,2-<i>b</i>:3,4-<i>b</i>′]­bis­(diseleno­[2,3-<i>b</i>:3′,2′-<i>d</i>]­selenophene) (<i>rac</i>-<b>2</b>) were prepared. The overall yields from selenophene were approximately 6.5 and 6.1%, respectively. Intermolecular interactions such as C–Se, C–S, and Se–Se were observed in the crystal packings of <i>rac-</i><b>1</b> and <i>rac-</i><b>2</b>. In addition, the absorption behaviors of <i>rac-</i><b>1</b> and <i>rac-</i><b>2</b> were investigated

Eryptosis as an Underlying Mechanism in Systemic Lupus Erythematosus-Related Anemia

Background: The progression of systemic lupus erythematosus (SLE) leads to anemia in patients, adversely affecting prognosis. The diverse causes of anemia may include excessive eryptosis or premature suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine (PS) exposure on the cell surface. The present study explored if SLE enhances eryptosis and the underlying mechanisms. Materials and Methods: Eryptosis was assessed using flow cytometry in healthy volunteers (n = 20) and anemic patients hospitalized for SLE (n = 22), for parameters including PS exposure, cell volume, cytosolic calcium ion (Ca2+) levels and reactive oxygen species (ROS) and ceramide abundance. These indicators were measured in erythrocytes of experimental subjects and erythrocytes treated with plasma from healthy volunteers or SLE patients. Results: The hemoglobin and hematocrit levels were significantly lower in anemic SLE patients than in healthy volunteers (***ppp2+ levels, oxidative stress. The measurements of PS and Ca2+ levels were significantly higher in the erythrocytes of healthy volunteers following incubation in plasma of SLE patients than in plasma of healthy volunteers for 24h (***ppConclusion: Eryptosis is enhanced in SLE and may contribute to anemia. The probable underlying mechanisms may be an excessive formation of ROS in erythrocytes. Also, some plasma components may trigger eryptosis by increasing the cytosolic Ca2+ concentration

Highly Cost-Effective Nitrogen-Doped Porous Coconut Shell-Based CO₂ Sorbent Synthesized by Combining Ammoxidation with KOH Activation

The objective of this research is to develop a cost-effective carbonaceous CO₂ sorbent. Highly nanoporous N-doped carbons were synthesized with coconut shell by combining ammoxidation with KOH activation. The resultant carbons have characteristics of highly developed porosities and large nitrogen loadings. The prepared carbons exhibit high CO₂ adsorption capacities of 3.44–4.26 and 4.77–6.52 mmol/g at 25 and 0 °C under atmospheric pressure, respectively. Specifically, the sample NC-650-1 prepared under very mild conditions (650 °C and KOH/precursor ratio of 1) shows the CO₂ uptake 4.26 mmol/g at 25 °C, which is among the best of the known nitrogen-doped porous carbons. The high CO₂ capture capacity of the sorbent can be attributed to its high microporosity and nitrogen content. In addition, the CO₂/N₂ selectivity of the sorbent is as high as 29, higher than that of many reported CO₂ sorbents. Finally, this N-doped carbon exhibits CO₂ heats of adsorption as high as 42 kJ/mol. The multiple advantages of these cost-effective coconut shell-based carbons demonstrate that they are excellent candidates for CO₂ capture