Search

Background: Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive., Methods: Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues., Results: Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM., Conclusion: Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications., (© 2024. The Author(s).)

Mindfulness-based interventions (MBIs) have been receiving growing attention in cancer care. This study evaluated the impact of the mindfulness-based stress reduction (MBSR) on quality of life, psychological distress (anxiety and depression), and cognitive emotion regulation strategies in patients with breast cancer under early chemotherapy. A total of 101 patients with breast cancer under early chemotherapy were randomly assigned to either an 8-week MBSR group (n = 50) or a control group (n = 51). The primary outcome was quality of life, measured on Functional Assessment of Cancer Therapy-Breast Cancer. The secondary outcomes were anxiety (Self-rating Anxiety Scale), depression (Self-rating Depression Scale), and cognitive emotion regulation strategies (The Chinese version of Cognitive Emotion Regulation Questionnaire). The participants were assessed at baseline (T0) and week 8 (T1). The data were statistically analyzed by SPSS 21.0. The participants in the MBSR group experienced significantly better outcomes in their quality of life, psychological distress, and cognitive emotion regulation strategies than the control group. The MBSR intervention was demonstrated to improve the positive cognitive emotion regulation strategies and quality of life in patients with breast cancer under early chemotherapy and significantly reduce the patient's anxiety, depression, and negative cognitive emotion regulation strategies, and help the patients to adjust their mental state and promote positive psychology to improve their quality of life., Competing Interests: The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The development of powerful and general methods to acquire ubiquitin (Ub) chains has prompted the deciphering of Ub-mediated processes. Herein, the cysteine-aminoethylation assisted chemical ubiquitination (CAACU) strategy is extended and improved to enable the efficient semi-synthesis of atypical Ub chain analogues and Ub-based probes. Combining the Cys aminoethylation and the auxiliary-mediated protein ligation, several linkage- and length-defined atypical Ub chains including di-Ubs, K27C-linked tri-Ub, K11/K48C-branched tri-Ub, and even the SUMOlated Ub are successfully prepared from recombinantly expressed starting materials at about a 9-20 mg L -1 expression level. In addition, the utility of this strategy is demonstrated with the synthesis of a novel non-hydrolyzable di-Ub PA probe, which may provide a new useful tool for the mechanistic studies of deubiquitinase (DUB) recognition., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An efficient method for the assembly of polyUb chains using auxiliary-modified Ub isomers is reported. This strategy takes advantages of auxiliary-mediated native chemical ligation between the distal Ub C-terminal hydrazide and the auxiliary of proximal Ub. Using removable protecting groups, Lys48-linked and Lys6-linked tri-Ub and even a mixed-linkage Lys6, Lys48-linked triUb in multimilligram quantities was made. These results demonstrate that this strategy yields natural polyubiquitin chains of desired length and linkage by using Ub isomer.

Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process.

Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation-desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, we describe an accelerated solid-phase synthetic protocol for ordinary or difficult peptides involving air-bath heating and amide protection. For the Hmsb-based backbone amide protection, an optimized acyl shift condition using 1,4-dioxane was discovered. The efficiency and robustness of the protocol was validated in the course of preparation of classical difficult peptides and ubiquitin protein segments.