Comment on “Network pharmacology and experimental validation reveal inhibition of the JAK2/STAT3 pathway by hydrogen sulfide in diabetic cardiomyopathy”
1Department of Anesthesiology, Heze Hospital Affiliated of Shandong First Medical University, Heze Municipal Hospital, Heze, Shandong, China
刊名
International Immunopharmacology
年份
2026
卷号
Vol.188
页码
117297
ISSN
1567-5769
摘要
Yang et al. investigated the protective effects of hydrogen sulfide against diabetic cardiomyopathy and proposed inhibition of JAK2/STAT3 signaling as a central mechanism. Their integration of network pharmacology with in vivo and in vitro experiments provides valuable evidence linking sodium hydrosulfide treatment to reduced myocardial inflammation and fibrosis. However, several issues may limit the causal interpretation of these findings. First, STAT3 prioritization was based on a small transc...更多
Yang et al. investigated the protective effects of hydrogen sulfide against diabetic cardiomyopathy and proposed inhibition of JAK2/STAT3 signaling as a central mechanism. Their integration of network pharmacology with in vivo and in vitro experiments provides valuable evidence linking sodium hydrosulfide treatment to reduced myocardial inflammation and fibrosis. However, several issues may limit the causal interpretation of these findings. First, STAT3 prioritization was based on a small transcriptomic dataset, nominal significance thresholds, and an exceptionally broad list of hydrogen sulfide–related targets. Second, the pharmacological rescue experiment lacked Colivelin-alone and clearly matched vehicle-control groups, making it difficult to distinguish pathway-specific reversal from the independent effects of Colivelin. Third, the high-glucose fibroblast experiments did not include an osmotic control. Finally, hydrogen sulfide bioavailability, endogenous hydrogen sulfide–producing enzymes, and systemic metabolic parameters were not assessed. Addressing these limitations through more rigorous bioinformatic thresholds, complete pharmacological controls, genetic validation, osmotic controls, and direct exposure measurements would strengthen the proposed mechanistic link between hydrogen sulfide, JAK2/STAT3 inhibition, and protection against diabetic cardiomyopathy.收起
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