Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx.

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702 cells.

Silver nanoparticles (AgNPs) are being used widely and increasingly in various products and medical supplies due to their antibacterial activity. However, little is known about the impacts of the AgNPs. Herein, The primary purpose of this study was to investigate the cytotoxic effect of AgNPs in the human liver cell line (HL-7702). The water-soluble α-Methoxy-poly (ethylene glycol)-ω-mercapto (mPEG-SH)-coated AgNPs (40 nm) were synthesized, which showed superior stabilization and uniform dispersion in culture medium. The effect of mPEG-SH-coated silver nanoparticles on cell viability, leakage of lactate dehydrogenase (LDH), oxidative stress, mitochondrial membrane potential (MMP), and cell cycle was evaluated after the cells were treated with nanoparticles. The results showed that the coated AgNPs could be taken up by cells, decreased cell viability in dose- and time-dependent manners at dosage levels between 6.25 and 100.00 µg/mL, caused membrane damage (LDH leakage), and decreased the activities of superoxide dismutase and glutathione peroxides. The level of malondialdehyde, an end product of lipid peroxidation, was also increased in AgNPs-exposed cells. Moreover, flow cytometric analysis showed that AgNP exposure decrease MMP and cause G2/M phase arrest. Thus, our data suggest that mPEG-SH-coated AgNPs have the potential toxicity that is associated with oxidative stress, apoptosis, and DNA damage.

New trimeric polyoxotungstate aggregates based on [P2W12O48]14- building blocks.

The first {P(2)W(12)}-based trimeric polyoxotungstates encapsulating various "guest" transition-metal and alkali-metal ions have been reported, exhibiting potentially aqua-ligand-induced capability of "trapping" metal ions.

Angiotensin-converting enzyme 2 inhibits high-mobility group box 1 and attenuates cardiac dysfunction post-myocardial ischemia.

High-mobility group box 1 (HMGB1) triggers and amplifies inflammation cascade following ischemic injury, and its elevated levels are associated with adverse clinical outcomes in patients with myocardial infarction (MI). Angiotensin-converting enzyme 2 (ACE2), a key member of vasoprotective axis of the renin-angiotensin system (RAS), regulates cardiovascular functions and exerts beneficial effects in cardiovascular disease. However, the association between HMGB1 and ACE2 has not been studied. We hypothesized that overexpression of ACE2 provides cardioprotective effects against MI via inhibiting HMGB1 and inflammation. ACE2 knock-in (KI) mice and littermate wild-type (WT) controls were subjected to either sham or coronary artery ligation surgery to induce MI. Heart function was assessed 4 weeks after surgery using echocardiography and Millar catheterization. Tissues were collected for histology and analysis of the expression of HMGB1, RAS components, and inflammatory cytokines. ACE2 in the heart of the ACE2 KI mice was 58-fold higher than WT controls. ACE2-MI mice exhibited a remarkable preservation of cardiac function and reduction of infarct size in comparison to WT-MI mice. Notably, ACE2 overexpression significantly reduced the MI-induced increase in apoptosis, macrophage infiltration, and HMGB1 and proinflammatory cytokine expression (TNF-α and IL-6). Moreover, in an in vitro study, ACE2 activation prevented the hypoxia-induced cell death and upregulation of HMGB1 in adult cardiomyocytes. This protective effect is correlated with downregulation of HMGB1 and downstream proinflammatory cascades, which could be useful for the development of novel treatment for ischemic heart disease.

Keggin-Type Polyoxometalate-Based Metal-Organic Networks for Photocatalytic Dye Degradation.

The reaction of Keggin-type polyoxometalate (POM) units, transition-metal (TM) ions, and a rigid bis(imidazole) ligand (1,4-bis(1-imidazolyl)benzene (bimb)) in a hydrothermal environment led to the isolation of four new POM-based metal-organic networks, [H2 L][CuL][SiW12 O40 ]⋅2 H2 O (1), [H2 L]2 [Co(H2 O)3 L][SiW11 CoO39 ]⋅6 H2 O (2), KH[CuL]2 [SiW11 CoO39 (H2 O)]⋅2 H2 O (3), and [CuL]4 [GeW12 O40 ]⋅H2 O (4; L=bimb). All four compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single-crystal X-ray diffraction. Compounds 1 and 3 are new 3D networks with 1D channels. Compounds 2 and 4 contain 2D networks, which further stack into 3D supramolecular networks. The contributions of pH value, the negative charge of the POM, and the TM coordination modes to the construction of 3D networks were elucidated by comparing the synthetic conditions and structures of compounds 1-4. The photocatalytic properties of compounds 1-4 were investigated using methylene blue (MB) degradation under UV light. All compounds showed good catalytic activity and structural stability. The possible catalytic mechanism was discussed on the basis of active-species trapping experiments. The different photocatalytic activities of compounds 1-4 were explained by comparison of the band gaps of different POM species and different packing modes of POM units in these hybrid compounds.

In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate.

A structural determined heteropolytungstate, [K(4)(H(2)O)(8)Cl][K(4)(H(2)O)(4)PTi(2)W(10)O(40)]·NH(2)OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The identity and high purity of compound 1 were confirmed by elemental analysis, NMR, IR analysis and single-crystal X-ray diffraction. The compound 1, evaluated in HepG 2.2.15 cells expressing permanently HBV, significantly reduced the levels of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. EC(50) values were determined to be 54µM for HBeAg, 61µM for HBsAg and 2.66µM for supernatant HBV DNA, as compared to 1671, 1570, 169µM, respectively, for the commercially-available hepatitis B drug adefovir dipivoxil (ADV). Intracellular cccDNA, pgRNA and HBcAg were also found to be decreased by compound 1 in a concentration-dependent manner. Cytotoxicity results showed that compound 1 has low toxicity in HepG 2 cells with CC(50) value of 515.20µM. The results indicate that compound 1 can efficiently inhibit HBV replication in HepG 2.2.15 cells line in vitro. Additionally, compound 1 also shows high anti-SARS activity at an EC(50) of 7.08µM and toxicity with a CC(50) of 118.6µM against MDCK cells.