Spike Protein Targeting "Nano-Glue" that Captures and Promotes SARS-CoV-2 Elimination

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant {beta}-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD < 1 pM) with negligible toxicity in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

RhoA/ROCK may involve in cardiac hypertrophy induced by experimental hyperthyroidism.

In this study, the role of the RhoA/Rho-kinase (RhoA/ROCK)-signaling pathway in cardiovascular dysfunction associated with hyperthyroidism was examined with the use of fasudil, a Rho-kinase inhibitor. Male Spraque-Dawley rats were treated with l-thyroxine (T(4)) alone, T(4) + low-dose fasudil (2 mg/kg/day) or T(4) + high-dose fasudil (10 mg/kg/day) and compared with control animals. Rats in the T(4) group showed an increase in the ratio of heart weight to body weight, which was ameliorated by fasudil at both low and high doses. Morphometric and hemodynamic parameters were also evaluated and confirmed that fasudil attenuated the cardiac hypertrophy induced by T(4). The extent of phosphorylation of the myosin phosphatase targeting subunit was quantified by Western blotting to evaluate the activity of Rho-kinase in the heart tissue. Both Western blotting and reverse transcriptase-polymerase chain reaction analyses revealed enhancement of Rho-kinase and activator protein 1 activity and reduction of c-FLIP(L) expression in the T(4) group, and this response was inhibited by fasudil in a dose-dependent manner. Furthermore, fasudil inhibited apoptosis induced by T(4) as evidenced by the detection of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and the expressions of bax and bcl-2. These results suggested that the RhoA/ROCK pathway is involved in the cardiac hypertrophy induced by experimental hyperthyroidism. The antagonism of this pathway may thus be useful as an alternative target in the treatment of hyperthyroid heart disease.

Effects of lipopolysaccharide on mice iron metabolism related genes mRNA expression / 解剖学报

ObjectiveTo investigate the effects of lipopolysaccharide (LPS) on mRNA expression of iron metabolism related genes. Methods Ten male mice (2 months) were injected intraperitoneally with lipopolysaccharide(0.5 μg/g). After 6 hours, mice were sacrificed and then sera, liver and spleen were collected. The mice blood routine was measured. The serum iron and total iron binding capacity (TIBC) were determined with reagent kit. The quasi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed for mRNA of hepatic hepcidin(HP), ferroportin1(Fpn1), transferrin receptor 1(TfR1) and spleenic HP, Fpn1 and interleukin-6(IL-6). Results The serum iron and TIBC were reduced in mice injected LPS, which exhibited mild anemia(P＜0.05) . LPS can increase the expression of hepatic hepcidin and decrease Fpn1 and TfR1 in liver after LPS administration 6 hours(P＜0.05). In spleen, IL-6 was upregulated and Fpn1 downregulated(P＜0.05). Conclusion LPS can influence serum iron through regulating the mRNA expression of hepatic and spleenic iron metabolism related genes, such as HP, Fpn1 and TfR1.

Stimulator of Fe transport and brain iron metabolism / 中国组织工程研究

OBJECTIVE: In order to understand the effect of stimulator of Fe transport(SFT) on Fe metabolism and its abnormality(absence or overloading),this study reviews the research development of SFT at home and abroad and focused on the relationship among expression,structure,physiological function,expressing controlling and expressing abnormality with brain iron metabolism.DATA SOURCES: Electronic literature search of NCBI related to SFT was performed using the terms "stimulator of iron transport" or "stimulator of Fe transport",and the language was restricted in English. And simultaneously CNKI database was searched with the word "brain iron metabolism" and"stimulator of Fe transport" in Chinese from January 1997 to October 2004.STUDY SELECTION: Articles that reported the structure,expression regulation of SFT and its relationship to brain iron metabolism diseases were included.DATA EXTRACTION: Twenty pieces of SFT-related literatures and 1300pieces of literatures related to brain iron metabolism were found,among which 21 pieces were included.DATA SYNTHESIS: From the 21 pieces of literatures,the structure,distribution,biological function,expression regulation of SFT and its relationship with brain iron metabolism were mainly discussed.CONCLUSION: SFT can stimulate both transferrin- and nontransferrin-bound iron uptake. The expression of SFT can be regulated transcriptionally and post-transcriptionally,mainly regulated in response to different cellular iron levels. So SFT plays an important role in brain iron metabolism.

Transferrin-bound Yb_2 uptake by U-87 MG cells and effect of Yb on proliferation of the cells / 中国病理生理杂志

AIM: To investigate the role of transferrin/transferrin receptor system in transferrin-bound Yb 2 (Yb 2Tf) uptake by U-87 MG cells and the effect of transferrin-bound and -free Yb 2 on proliferation of U-87 MG cells. METHODS: Cell culture and ICP-MS measurement of Yb 2. RESULTS: Yb 2Tf uptake by U-87 MG cells increased with the concentrations of Yb 2Tf, and reached saturation as the concentration in the incubation medium was raised to about 2 ?mol/L. Also, Yb 2 uptake by the cells increased with increase of the mole ratio (Yb 2: apoTf), reaching a maximum at 1.5 mole ratio. Yb 2Tf in 0.4 ?mol/L significantly inhibited proliferation of U-87 MG cells, however, 10 ?mol/L Yb 3+ had no significant effect on proliferation of the cells. CONCLUSION: The uptake of Yb 2 by U-87 MG cells might be mediated by transferrin/transferrin receptor system. Transferrin-bound but not transferrin-free Yb 2 could significantly inhibit proliferation of U-87 MG cells.

Hepcidin and iron homeostasis / 中华内分泌代谢杂志

The understanding of iron metabolism in humans, especially of its mechanism involved in controlling iron absorption in the proximal small intestine, is of great importance since diseases associated with iron deficiency or overload are very common worldwide. Recent study on hepcidin which is senthesized by liver has showed that this originally identified as a circulating antimicrobial peptide is a putative iron regulatory hormone. It plays a central role in the regulation of small intestine iron absorption and body iron homeostasis. The increased expression of hepcidin in the liver, induced by inflammation, might be an initial cause of the anemia of infection or chronic diseases and the iron-overload diseases might be tightly associated with the decreased hepcidin expression in the liver.

THE INFLUENCE OF Fe~(3+) ON Ca~(2+) AND THE RELATIONSHIP BETWEEN Ca~(3+) AND THE CELL APOPTOSIS IN Caco-2 CELLS / 解剖学报

Objective To study the influence of ion concentration change out of cells on calcium transportation and the relationship between the rising of calcium concentration in the Caco-2 cells and its apoptosis to offer the theoretical and experimental bases for clinical study and digestive tract physiology and patholoogy. Methods Confocal laser scanning microscope(CLSM) and flow cytometry(FCM) were used in this study. Results (1) Diversion of Ca 2+ into cells was increased with the decrease of Fe 3+ concentration out of Caco-2 cells(the final consistence of DFO was 100-300??mol/L),but was hindered with the increase of Fe 3+ concentration out of them(the final consistence fo FAC was 10-100??mol/L) as observed under CLSM; (2) The cell state was fine and its viability was more than 90% as observed under CLSM after treated by A 23187 and Fluo-3/AM(examined with FDA);(3) The Ca 2+ concentration in the Caco-2 cells was increased by A 23187 and this function was dose depended.The Caco-2 cell apoptosis was induced by the increase of Ca 2+ in cells,which was examined with FCM.Conclusion The Ca 2+ transportation was increased with the decrease of Fe 3+ concentration out of Caco-2 cells but was hindered with the increase of Fe 2+ concentration out of them.The Caco-2 cell apoptosis was induced by the increase of Ca 2+ concentration in them.