structural-biology-analytical-chemistry-approaches-for-characterizing

Structural Biology and Analytical Chemistry Approaches for Characterizing <em>C</em>-Glycoside Metabolic Enzymes in Human Gut Microbiota

The gut microbiota has emerged as a key modulator of host health, particularly because of its capacity to metabolize dietary glycosides. While ...

Beijing University of Chinese Medicine

Ferroptosis is an iron-dependent regulation of cell death driven by lipid peroxidation, which is intracellularly dependent on iron and independent of other metals, and morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. Ferroptosis is closely related to physiological and pathological processes, such as development, aging, and immunity, and it plays an important role in a variety of diseases. In many departments, traditional Chinese medicine plays an increasingly important role in their clinical treatment. In recent years, an increasing number of studies have been conducted on the mechanism of ferroptosis in traditional Chinese medicine. However, the role of ferroptosis in the clinical treatment of traditional Chinese medicine requires further exploration. This article mainly introduces the application of ferroptosis in studies of the mechanism of traditional Chinese medicine to help clinicians understand the current status of traditional Chinese medicine therapy for the treatment of ferroptosis-related diseases.

Mechanism of ferroptosis in traditional chinese medicine for clinical treatment: A review.

The -glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of -glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the -glycosidic bond of puerarin (daidzein-8--glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a -glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting - to -glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated -glycosidic bond breakage and formation, but also may help to facilitate stereospecific -glycoside synthesis in pharmaceutical industry.

Structural mechanism of a dual-functional enzyme DgpA/B/C as both a -glycoside cleaving enzyme and an - to -glycoside isomerase.

 an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor.

While targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain.

Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study.

The aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease.

Association of different domains of physical activity with diabetic kidney disease: a population-based study.

Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition.

Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network meta-analysis.

The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM).

Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study.

The role of immune cells in the pathogenesis and advancement of diabetic nephropathy (DN) is crucial. The objective of this study was to identify immune-cell-related biomarkers that could potentially aid in the diagnosis and management of DN.

VCAM1: an effective diagnostic marker related to immune cell infiltration in diabetic nephropathy.

The oxidative balance score (OBS) is a comprehensive concept that includes 16 dietary components and four lifestyle factors to assess an individual's exposure to pro-oxidants and antioxidants. This study aims to explore the relationship between OBS and the risk of chronic kidney disease (CKD).

Association between chronic kidney disease and oxidative balance score: National Health and Nutrition Examination Survey (NHANES) 2005-2018.

The C-reactive protein/Lymphocyte Ratio (CLR) is a novel biomarker whose role in the development of chronic kidney disease (CKD) is not well understood. This study aimed to investigate the correlation between CLR and the prevalence of CKD.

The relationship between C-reactive protein to lymphocyte ratio and the prevalence of chronic kidney disease in US adults: a cross-sectional study.

The Oxidative Balance Score (OBS) quantifies the overall oxidative stress burden, with higher scores indicating greater antioxidant (relative to prooxidant) activity. This study aimed to examine the association between peripheral arterial disease (PAD) and OBS.

Association between oxidative balance scores and peripheral artery disease in US adults: a cross-sectional study.

It has been regarded as an essential treatment option for diabetic nephropathy (DN) in Traditional Chinese medicine. Previous studies have demonstrated the anti-DN efficacy of Schisandra chinensis Fruit Mixture (SM); however, a comprehensive chemical fingerprint is still uncertain, and its mechanism of action, especially the potential therapeutic targets of anti-DN, needs to be further elucidated.

Integrated UPLC-ESI-MS/MS, network pharmacology, and transcriptomics to reveal the material basis and mechanism of Schisandra chinensis Fruit Mixture against diabetic nephropathy.

Diabetic patients are highly susceptible to cardiovascular and renal diseases. As a newly updated comprehensive index for assessing cardiovascular health (CVH), Life's essential 8 (LE8) has the potential to serve as a practical tool for evaluating the risk of diabetic kidney disease (DKD). We are committed to exploring the relationship between LE8 and its subscales with DKD in diabetic patients, aiming to provide preliminary evidence for the formulation of clinical strategies.

Article	Year
Mechanism of ferroptosis in traditional chinese medicine for clinical treatment: A review. Frontiers in pharmacology\| PubMed ID: 36686700	2022
Structural mechanism of a dual-functional enzyme DgpA/B/C as both a -glycoside cleaving enzyme and an - to -glycoside isomerase. Acta pharmaceutica Sinica. B\| PubMed ID: 36815035	2023
SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor. Acta pharmaceutica Sinica. B\| PubMed ID: 37360012	2023
Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study. Frontiers in immunology\| PubMed ID: 37711613	2023
Association of different domains of physical activity with diabetic kidney disease: a population-based study. Frontiers in endocrinology\| PubMed ID: 38863925	2024
Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network m... Renal failure\| PubMed ID: 38967189	2024
Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional stud... Frontiers in endocrinology\| PubMed ID: 39145317	2024
VCAM1: an effective diagnostic marker related to immune cell infiltration in diabetic nephropathy. Frontiers in endocrinology\| PubMed ID: 39319258	2024
Association between chronic kidney disease and oxidative balance score: National Health and Nutrition Examination Survey (NHANES) 2005-2018. Frontiers in nutrition\| PubMed ID: 39830066	2024
The relationship between C-reactive protein to lymphocyte ratio and the prevalence of chronic kidney disease in US adults: a cross-sectional study. Frontiers in endocrinology\| PubMed ID: 39882264	2024
Association between oxidative balance scores and peripheral artery disease in US adults: a cross-sectional study. Frontiers in nutrition\| PubMed ID: 39897536	2024
Integrated UPLC-ESI-MS/MS, network pharmacology, and transcriptomics to reveal the material basis and mechanism of Schisandra chinensis Fruit Mixture against diabetic nephropathy. Frontiers in immunology\| PubMed ID: 40046619	2024
Association between life's essential 8 and diabetic kidney disease: a population-based study. Renal failure\| PubMed ID: 40064556	2025

Pengfei He

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