CTH and hyperhomocysteinemia: Luo et al. (2021) established a hyperhomocysteinemia (HHcy) model using a high-methionine diet, discovering that Hcy accumulation impaired CSE activity, increased CSE nitration, and reduced H2S production. This deficiency in H2S diminished Sp1 S-sulfhydration and its binding to the CSE promoter, downregulating CSE and further decreasing H2S, thus disrupting the Hcy trans-sulfuration pathway and raising serum Hcy levels. The H2S donor GYY4137 lowered homocysteine levels, increased Sp1 S-sulfhydration levels, and restored Sp1-CSE-H2S pathway function.