Drugs for metabolic diseases usually require systemic administration and act on multiple tissues, which may produce some unpredictable side effects. There have been many successful studies on targeted drugs, especially antitumor drugs. However, there is still little research on metabolic disease drugs targeting specific tissues. Fibroblast growth factor 1 (FGF1) is a potential therapy for type 2 diabetes (T2D) without the risk of hypoglycemia. However, the major impediment to the clinical application of FGF1 is its mitogenic potential. We previously engineered an FGF1 variant (named FGF1ΔHBS) to tune down its mitogenic activity via reducing the heparin-binding ability. However, other notable side effects still remained, including severe appetite inhibition, pathogenic loss of body weight, and increase in fatality rate. In this study, we used AlphaFold2 and PyMOL visualization tools to construct a novel FGF1ΔHBS conjugate fused with skeletal muscle-targeted (MT) peptide through a flexible peptide linker termed MT-FGF1ΔHBS. We found that MT-FGF1ΔHBS specifically homed to skeletal muscle tissue after systemic administration and induced a potent glucose-lowering effect in T2D mice without hypoglycemia. Mechanistically, MT-FGF1ΔHBS elicits the glucose-lowering effect via AMPK activation to promote the GLUT4 expression and translocation in skeletal muscle cells. Notably, compared with native FGF1ΔHBS, MT-FGF1ΔHBS had minimal effects on food intake and body weight and did not induce any hyperplasia in major tissues of both T2D and normal mice, indicating that this muscle-homing protein may be a promising candidate for T2D treatment. Our targeted peptide strategy based on computer-aided structure prediction in this study could be effectively applied for delivering agents to functional tissues to treat metabolic or other diseases, offering enhanced efficacy and reducing systemic off-target side effects.

Background Psoas hematoma rarely occurs in patients with spondylolisthesis who undergo posterior lumbar interbody fusion (PLIF) surgery. Case presentation Here we reported a case of a 57-year-old male patient diagnosed with spondylolisthesis who underwent PLIF at the local hospital. Seven days post-surgery, abdominal pain occurred, and the pain in the right lower limb gradually increased. The computerized tomography (CT) indicated a formation of hematoma around the psoas muscle. Digital-subtraction angiography (DSA) suggested a vascular injury, a rupture of the right segmental artery of the lumbar vertebral level 4. The patient then received DSA vascular embolization, after which the lower lumbar segmental artery active bleeding was stopped. One month after discharge, the abdominal hematoma was gradually absorbed, and the pain in the waist, leg, and abdomen disappeared. Conclusion Symptoms such as abdominal pain, abdominal distension, and exacerbation of lower limb pain, may suggest the occurrence of psoas hematoma after PLIF. DSA vascular embolization is suggested as the first treatment approach for this type of complication.