natural-products-inhibiting-necroptosis-molecular-mechanisms

Natural Products Inhibiting Necroptosis: Molecular Mechanisms and Therapeutic Opportunities

Necroptosis is a genetically regulated form of necrotic cell death initiated by diverse signals, including death receptor ligands, which activate the ...

Chengdu University of Traditional Chinese Medicine

Computerized interpretation of electrocardiogram plays an important role in daily cardiovascular healthcare. However, inaccurate interpretations lead to misdiagnoses and delay proper treatments. In this work, we built a high-quality Chinese 12-lead resting electrocardiogram dataset with 15,357 records, and called for a community effort to improve the performances of CIE through the China ECG AI Contest 2019. This dataset covers most types of ECG interpretations, including the normal type, 8 common abnormal types, and the other type which includes both uncommon abnormal and noise signals. Based on the Contest, we systematically assessed and analyzed a set of top-performing methods, most of which are deep neural networks, with both their commonalities and characteristics. This study establishes the benchmarks for computerized interpretation of 12-lead resting electrocardiogram and provides insights for the development of new methods. Graphical Abstract A community effort to assess and improve computerized interpretation of 12-lead resting electrocardiogram.

A community effort to assess and improve computerized interpretation of 12-lead resting electrocardiogram.

The gut microbiota and its metabolic activities are crucial for maintaining host homoeostasis and health, of which the role of probiotics has indeed been emphasized. The current study delves into the performance of probiotics as a beneficial managemental strategy, which further highlights their impact on growth performance, serologic investigation, gut microbiota, and metabolic profiling in yaks' calves. A field experiment was employed consisting of 2 by 3 factorial controls, including two development stages, namely, 21 and 42 days (about one and a half month), with three different feeding treatments. Results showed a positive impact of probiotic supplements on growth performance by approximately 3.16 kg (< 0.01) compared with the blank control. Moreover, they had the potential to improve serum antioxidants and biochemical properties. We found that microorganisms that threaten health were enriched in the gut of the blank control with the depletion of beneficial bacteria, although all yaks were healthy. Additionally, the gut was colonized by a microbial succession that assembled into a more mature microbiome, driven by the probiotics strategy. The gut metabolic profiling was also changed significantly after the probiotic strategy, i.e., the concentrations of metabolites and the metabolic pattern, including enrichments in protein digestion and absorption, vitamin digestion and absorption, and biosynthesis of secondary metabolites. In summary, probiotics promoted gut microbiota/metabolites, developing precise interventions and achieving physiological benefits based on intestinal microecology. Hence, it is important to understand probiotic dietary changes to the gut microbiome, metabolome, and the host phenotype.  The host microbiome is a composite of the trillion microorganisms colonizing host bodies. It can be impacted by various factors, including diet, environmental conditions, and physical activities. The yaks' calves have a pre-existing imbalance in the intestinal microbiota with an inadequate feeding strategy, resulting in poor growth performance, diarrhea, and other intestinal diseases. Hence, targeting gut microbiota might provide a new effective feeding strategy for enhancing performance and maintaining a healthy intestinal environment. Based on the current findings, milk replacer-based  feeding may improve growth performance and health in yaks' calves.

Effects of Milk Replacer-Based  on Growth and Gut Development of Yaks' Calves: a Gut Microbiome and Metabolic Study.

 The involvement of glycolysis in the regulation of the tumor immune microenvironment has become a novel research field. In this study, the specific functions and clinical significance of glycolysis-related genes (GRGs) and immune-related genes (IRGs) were systematically characterized in lung squamous cell carcinoma (LUSC).  We evaluated the prognostic value, interactions, somatic mutations, and copy-number variations of GRGs and IRGs in LUSC from a dataset of The Cancer Genome Atlas (TCGA). An integrated glycolysis-immune score (GIS) model was generated by random forest algorithm and stepwise Cox regression analysis. The predictive power of the GIS was examined by survival analysis, receiver operating characteristics, univariate and multivariate analyses, and subgroup analysis. The correlations between GIS and biological functions, glycolysis, immune activity, immune cell infiltration, and genomic changes were analyzed, and the potential of GIS to guide clinical treatment decisions was evaluated.  A total of 54 prognostic GRGs and IRGs were identified, and a strong correlation was noted among them. However, most of them had somatic mutations and a high incidence of CNV. The GIS model that contained two GRGs ( and ) and three IRGs (, , and ) was generated and a high GIS indicated poor survival. Moreover, we found that low GIS was associated with immune pathway activation, M1 macrophage infiltration, and higher immune scores. Finally, patients with low GIS were more sensitive to chemotherapy and immunotherapy.  An integrated model based on glycolysis and immune genes can distinguish the biological functions and immune infiltration patterns of individual tumors, quantitatively estimate the prognosis of patients with LUSC, and guide chemotherapy and immunotherapy decisions.

Development and validation of a combined glycolysis and immune prognostic signature for lung squamous cell carcinoma.

The aim of this study was to develop and validate a machine learning-based predictive model that predicts 90-day mortality in ICU trauma patients.

A Retrospective Cohort Study: Predicting 90-Day Mortality for ICU Trauma Patients with a Machine Learning Algorithm Using XGBoost Using MIMIC-III Database.

Sea buckthorn (Hippophae rhamnoides), a traditional Tibetan medicinal herb, exhibits protective effects against cardiovascular and respiratory diseases. Although Sea buckthorn extract (SBE) has been confirmed to alleviate airway inflammation in mice, its therapeutic effect and underlying mechanism on chronic obstructive pulmonary disease (COPD) requires further clarification.

Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways.

Cichorium intybus is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in C. intybus. However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects require further elucidation.

Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2.

The stimulator of interferon genes (STING) pathway plays a critical role in inflammatory diseases like ulcerative colitis (UC), yet no STING inhibitors are clinically available. Toosendanin (TSN), a bioactive triterpenoid from fruits of Melia toosendan, has been shown to ameliorate UC, though its exact molecular targets and detailed mechanisms remain unclear. This study investigates whether TSN inhibits STING pathway activation to alleviate UC and identifies potential target proteins involved in suppressing STING signaling. Herein, we first confirmed TSN's suppression of STING-dependent genes, including interferon-beta1 (IFNB1), C-X-C motif chemokine 10 (CXCL10), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in murine RAW264.7 and human THP-1 differentiated macrophages activated by herring testis DNA (HT-DNA), 5,6-dimethylxantheonone-4-acetic acid (DMXAA), or cyclic GMP-AMP (cGAMP). Furthermore, TSN also suppressed phosphorylation of STING, TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), nuclear factor kappa-B (NF-κB) p65 induced by HT-DNA, DMXAA, or cGAMP, while preventing DMXAA-induced nuclear translocation of IRF3 and p65 in RAW264.7 cells. Mechanistically, TSN could not only directly bind Lck/Yes-related novel protein tyrosine kinase (LYN) to reduce DMXAA-induced phosphorylation of LYN and protein kinase B (AKT), but also directly interacted with STING protein to inhibit its oligomerization, thereby inhibiting STING pathway activation. In vivo, TSN ameliorated dextran sulfate sodium (DSS)-induced colitis in mice via downregulating STING pathway components. These findings demonstrated that TSN achieved its anti-inflammatory effects by suppressing the STING pathway through direct binding to both LYN and STING proteins, suggesting its therapeutic potential for UC and other conditions involving aberrant STING activation.

Toosendanin inhibits STING signaling pathway to alleviate ulcerative colitis via blocking LYN kinase and STING protein.

Spontaneous pneumothorax (SP) is a recurrent and debilitating complication in cystic lung diseases (CLD), often requiring invasive interventions and multidisciplinary respiratory rehabilitation (MRR). However, evidence regarding the role of MRR in post-pneumothorax recovery remains limited.

Multidisciplinary respiratory rehabilitation after spontaneous pneumothorax in cystic lung disease: a case report with literature review.

Necroptosis exacerbates ulcerative colitis (UC) by disrupting intestinal barriers and promoting necroinflammation. Heat shock protein 90 (HSP90) regulates receptor-interacting protein kinase 1/3 (RIPK1/3) activity through its chaperone function, thereby participating in necroptosis and emerging as a potential therapeutic target for its inhibition in UC therapy. Costunolide (CTL), a principal sesquiterpene lactone from Aucklandia lappa, has poorly defined mechanisms in UC treatment. This study aimed to elucidate CTL's role in necroptosis inhibition and UC therapy by targeting HSP90.

Article	Year
A community effort to assess and improve computerized interpretation of 12-lead resting electrocardiogram. Medical & biological engineering & computing\| PubMed ID: 34677739	2022
Effects of Milk Replacer-Based on Growth and Gut Development of Yaks' Calves: a Gut Microbiome and Metabolic Study. Microbiology spectrum\| PubMed ID: 35771011	2022
Development and validation of a combined glycolysis and immune prognostic signature for lung squamous cell carcinoma. Frontiers in genetics\| PubMed ID: 36246596	2022
A Retrospective Cohort Study: Predicting 90-Day Mortality for ICU Trauma Patients with a Machine Learning Algorithm Using XGBoost Using MIMIC-III Database. Journal of multidisciplinary healthcare\| PubMed ID: 37701177	2023
Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways. Journal of ethnopharmacology\| PubMed ID: 39181279	2025
Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2. Journal of ethnopharmacology\| PubMed ID: 39904423	2025
Toosendanin inhibits STING signaling pathway to alleviate ulcerative colitis via blocking LYN kinase and STING protein. Biochemical pharmacology\| PubMed ID: 41187884	2026
Multidisciplinary respiratory rehabilitation after spontaneous pneumothorax in cystic lung disease: a case report with literature review. Respiratory medicine case reports\| PubMed ID: 41488043	2026
Covalently targeting HSP90 with a natural small-molecule costunolide to inhibit necroptosis and ulcerative colitis. International immunopharmacology\| PubMed ID: 41687519	2026

Shan Yang

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