Ferroptosis in diabetic cardiomyopathy: from its mechanisms to therapeutic strategies.

Diabetic cardiomyopathy (DCM) is defined as structural and functional cardiac abnormalities in diabetes, and cardiomyocyte death is the terminal event of DCM. Ferroptosis is iron-dependent oxidative cell death. Evidence has indicated that iron overload and ferroptosis play important roles in the pathogenesis of DCM.

Replacement Dose for Overt Hypothyroidism Induced by Programmed Cell Death Protein 1 Antibodies May Be Higher than Recommended.

Background: The present recommendations, consensus, or guidelines for the replacement dosage for hypothyroidism induced by programmed cell death protein 1 (PD-1) therapy are not uniform, and there are very few special clinical trials that have examined the replacement dosage for it.

Objectives: This article illustrates the clinical characteristics of hypothyroidism induced by PD-1 antibodies (Abs) and reports the recommended replacement dosage for hypothyroidism.

Methods: Eighteen patients with overt primary hypothyroidism induced by PD-1 Abs (group 1) were selected from 655 patients with different tumor types.

Unveiling the advantages of an ultrathin N-doped carbon shell on self-supported tungsten phosphide nanowire arrays for the hydrogen evolution reaction experimentally and theoretically.

Packaging electrocatalysts with carbon shells offers an opportunity to develop stable and effective hydrogen evolution reaction (HER) materials. Here, an ultrathin N-doped carbon-coated self-supported WP nanowire array (WP@NC NA) hybrid has been synthesized. Owing to the encapsulation of the ultrathin N-doped carbon shell on the WP surface, the as-prepared WP@NC NA hybrid exhibits enhanced physicochemical stability, more active sites, and superior conductivity compared with WP NA without carbon coating.

[Progress in the mechanisms of response to different oxygen concentrations in Caenorhabditis elegans].

Oxygen levels are unequal in different living geographical locations of human and related to normal physiology of health. The reduction of oxygen level in the body can lead to a variety of diseases, such as stroke caused by cerebral ischemia and hypoxia. In the recent years, many studies have elucidated the molecular and cellular mechanisms of organism response to different oxygen concentrations by using the nematode Caenorhabditis elegans (C.

A novel COL10A1 mutation in a Chinese pedigree with Schmid type metaphyseal chondrodysplasia.

Background: Schmid type metaphyseal chondrodysplasia (MCDS) is a kind of autosomal inherited epiphyseal dysplasia caused by a mutation of the COL10A1 gene. Clinical expression of this mutation includes a waddling gait, coxa vara, genu varus or genu valgus and shortened lower limbs among others. To date, over 40 kinds of heterozygous mutations have been identified in the collagen domain of COL10A1 but data on family pedigrees for these is lacking.

Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids.

A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH(3), CH(3), and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn(2+) but did not result in enhancement in potency.

Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.

Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays.

Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties.

We have screened molecules for inhibition of MetAP2 as a novel approach toward antiangiogenesis and anticancer therapy using affinity selection/mass spectrometry (ASMS) employing MetAP2 loaded with Mn(2+) as the active site metal. After a series of anthranilic acid sulfonamides with micromolar affinities was identified, chemistry efforts were initiated. The micromolar hits were quickly improved to potent nanomolar inhibitors by chemical modifications guided by insights from X-ray crystallography.

3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).

Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2.

Methionine aminopeptidase (MetAP)-2 has been suggested as a novel target for cancer therapy because the anticancer agent TNP-470 irreversibly inactivates the catalytic activity of this enzyme. However, the importance of MetAP2 in cell growth and tumor progression was uncertain because previous data were based on the chemically reactive TNP-470. Here we show that a rationally designed reversible MetAP2 inhibitor, A-357300, suppresses tumor growth preclinically without the toxicities observed with TNP-470.

Physiologically relevant metal cofactor for methionine aminopeptidase-2 is manganese.

The identity of the physiological metal cofactor for human methionine aminopeptidase-2 (MetAP2) has not been established. To examine this question, we first investigated the effect of eight divalent metal ions, including Ca(2+), Co(2+), Cu(2+), Fe(2+), Mg(2+), Mn(2+), Ni(2+), and Zn(2+), on recombinant human methionine aminopeptidase apoenzymes in releasing N-terminal methionine from three peptide substrates: MAS, MGAQFSKT, and (3)H-MASK(biotin)G. The activity of MetAP2 on either MAS or MGAQFSKT was enhanced 15-25-fold by Co(2+) or Mn(2+) metal ions in a broad concentration range (1-1000 microM).

Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly.

Many conventional chemotherapeutics, such as the microtubule-stabilizing anticancer drug paclitaxel (Taxol), have been shown to have anti-angiogenic activity and clinical application of a continuous low dose of these agents has been suggested for cancer therapy. In this study, we show that paclitaxel selectively inhibits the proliferation of human endothelial cells (ECs) at ultra low concentrations (0.1-100 pM), with an IC50 = 0.