Palladium (II), platinum (II) and silver (I) complexes with oxazolines: Their synthesis, characterization, DFT calculation, molecular docking and antitumour effects.

Six new Pd(II), Pt(II) and Ag(I) complexes, (1);{Pd (L1)]2C6H4}2Cl4} (2); Pt(L2)(DMSO)Cl; 3; {PtL5]2C6H4}2·PhCOO-⋅11NO3-; 4; {[Pt(L4)]2C6H4}; the binuclear cyclometalated complex the polymer chain (5); {[PtL5]C6H4}·NO3-}; and the polymeric silver species (6); Zn(L6)2·AgNO3·CHCl3 were synthesized and thoroughly characterized using X-ray diffraction and spectroscopic techniques (L1=(S,S)-1,4-i-PrOx]2C6H4}2Cl4, L2=Di(2,2-bis(4R-isopropyl-4,5-dihydro-oxazol-2-yl)acetonitrile) zinc (II) (BR1);L3= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene (AR2); L4= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene，L5=1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)-benzene，L6=Di(2,2-bis(4S-isopropyl-4,5-dihydrooxazol-2-yl)acetonitrile) zinc (II). Complexes 1-6 showed cytotoxic effects against human tumour cell lines, including a multidrug-resistant subline. Oxazoline and Pd complex 1 induced apoptosis in A549 cells. DFT calculations were also performed to exhibit the excellent bioactivity of complex 1 against A549, MDA-MB-231, and KB cells. Complex 1, with the best docking score and a stable interaction network within the binding site of the G-quadruplex, could stably interact with the G-quadruplex. Additionally, complex 1 was further used in the animal experiment of human lung adenocarcinoma cells in nude mice. By comparing with the model control group, the tumour volume, relative tumour volume and relative tumour proliferation rate T/C decreased significantly in the cisplatin group and compound 1 (complex 1) group.

A successful case of electrical storm rescue after acute myocardial infarction.

BACKGROUND: Electrical storm (ES) is a heterogeneous clinical emergency that can present with malignant ventricular arrhythmias such as ventricular fibrillation (VF), ventricular tachycardia (VT), requiring the need for cardiac defibrillation. ES is a life-threatening condition with a high mortality rate. Successfully managing ES in the setting of acute myocardial infarction (MI) is expected to be known by physicians on call to reduce in-hospital mortality. CASE PRESENTATION: A 57-year-old man presenting with acute onset chest pain was found to have an infero-posterior ST-segment elevation myocardial infarction (STEMI) complicated by acute right ventricular MI secondary to total occlusion of the proximal right coronary artery (RCA). The patient developed ES in the form of recurrent VF that was managed successfully with electrical defibrillation, antiarrhythmic therapy with amiodarone and esmolol, endotracheal intubation, sedation, electrolyte replacement, volume resuscitation, comfort care, psychological intervention, and percutaneous coronary intervention (PCI) of the occluded epicardial artery. With these interventions used in quick succession and with the aspiration of a massive RCA thrombus, the patient was reversed to hemodynamic stability, did not have further episodes of VF, and survived the index hospitalization. CONCLUSION: ES is a rare but fatal complication of acute MI. Residents on night shifts should be better prepared and equipped to deal with this rare condition. We hope our successful experience can benefit physicians on call who take care of acute MI patients that deteriorate with ES.

Synthesis and biological evaluation of mixed-ligand cyclometalated iridium(III)-quinoline complexes.

With the aim of gaining new insight into the underlying apoptosis mechanisms and in vivo efficacy of cyclometalated Ir(III) complexes as metalodrugs, six new cyclometalated Ir(III)-quinoline complexes, [Ir(1a)(2pq)2] (2a), [Ir(1b)(2pq)2] (2b), [Ir(1c)(2pq)2] (2c), [Ir(1d)(2pq)2] (2d), [Ir(1e)(2pq)2] (2e), and [Ir(1f)(2pq)2] (2f) (2pq = 2-phenylisoquinoline), have been synthesized using 5,7-dihalo-8-hydroxylquinoline ligands (1a-1f) and [Ir(2pq)2Cl]2 precursors and characterized. Complexes 2a-2f have shown potent anticancer activity against cisplatin-resistant SK-OV-3/DDP and A549/DDP cells (IC50 = 0.11-1.83 µM), following the order 2e > 2f > 2b > 2c > 2d > 2a. Confocal microscopy images suggest that 2e and 2b could act as red-color probes for specific cell imaging and efficiently initiate apoptosis and autophagy in the mitochondria, cell cytosol, and nucleus. Overexpression of beclin1, caspase-9, cytochrome c, LC3II, and apaf-1; inhibition of p62, cyclin D1, cyclin A2, and CDK2; and a substantial rapid accumulation suggest a paraptotic mode of cell death induced by autophagy, DNA damage, and mitochondrial stress. In addition, the inhibitory rate of 2e on A549/DDP tumor growth was 64.1% at a concentration of 10.0 mg kg-1, which is clearly higher than that of cisplatin. According to the biological assay, the cyclometalated Ir(III)-quinoline complex 2e exhibited a higher anticancer effect than 2b, which may be associated with the electronic effect of the methyl group of the 1e ligand of 2e playing a key role in the mechanism.

An electrochemical biosensor based on the enhanced quasi-reversible redox signal of prussian blue generated by self-sacrificial label of iron metal-organic framework.

We develop for the first time a new electrochemical biosensor for signal-on detection of T4 polynucleotide kinase (PNK) based on the enhanced quasi-reversible redox signal of prussian blue generated by self-sacrificial label of iron metal-organic framework (FeMOF). The DNA hairpin probe modified with FeMOF@AuNPs at the 3'-thiol end acts as the substrate of PNK. The presence of PNK enables the 5'-phosphorylation of hairpin probe, which may subsequently function as the substrate of lambda exonuclease. Lambda exonuclease removes the 5' mononucleotides from the stem, unfolding the hairpin structure and releasing the single-stranded DNA (ssDNA). The resultant FeMOF@AuNP-modified ssDNA may specifically hybridize with the capture probe to form the double-strand DNA (dsDNA) duplex, enabling the immobilization of FeMOF on the electrode surface. The reaction of Fe3+ in the MOF with K4Fe(CN)6 leads to the formation of prussian blue on the electrode surface and consequently the generation of a high electrochemical signal. This assay is very simple without the involvement of the pre-synthesized prussian blue which is unstable in neutral buffer, and the self-sacrificial label of FeMOF can achieve great signal amplification without the involvement of any extra functional materials. Due to the introduction of self-sacrificial label of FeMOF and the formation of prussian blue nanolayers with good quasi-reversible cyclic voltammetric electrochemical activity, this biosensor exhibits high sensitivity and a large dynamic range. Moreover, this biosensor can be used to screen the PNK inhibitors, holding great potential in disease diagnosis and drug discovery.

Exacerbation of chronic inflammatory diseases by infectious agents: Fact or fiction?

Chronic inflammatory diseases caused by obesity represent critical public health concerns worldwide. In these diseases such as metabolic syndrome, diabetes and atherosclerosis, adipose tissue acts as an endocrine organ that releases large quantities of inflammatory mediators into circulation. Besides classically recognized effectors on the development of obesity and resultant conditions, infection has attracted attention as an enhancer of chronic inflammatory diseases. Infectious diseases have long been associated with obesity, metabolic syndrome, diabetes and atherosclerosis. However, the infectious hypothesis for chronic inflammatory diseases has been challenged by inconclusive clinical trials. Nevertheless, the large body of evidence accumulated over decades on the association of infectious diseases with obesity, diabetes and cardiovascular disease should not be disregarded. Instead, re-formulation of hypotheses of the mechanisms by which microbes affect obesity-associated diseases may be required with an emphasis on the early events in the progression of such diseases and the multifactorial nature of pathogen-host interactions. This review focuses on pathogens that directly promote obesity and on pathogens that cause chronic infections and thereby enhance metabolic diseases in obese patients. A new perspective on the interaction between infections and obesity-related diseases may improve management of chronic inflammatory diseases that rank high among global threats to human health.