This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective:This clinical study describes the surgical methods and clinical effects for large skin and soft tissue defects of the extremities.Methods:Between October 2005 and February 2019, the patients with large skin and soft tissue defects of the extremities were hospitalized in the Department of Hand Surgery of the Orthopedic Hospital of Taizhou. The choice of flaps for primary phase repair was determined by the degree and the type of defect, including anterolateral thigh (ALT) flap, latissimus dorsi myocutaneous flap (LDMF), combined free ALT flap and osteocutaneous fibula flap and vascularized iliac osteocutaneous flap based on superficial circumflex iliac artery (SCIA). The donor site was primarily closed. And the appearance and function of donor and recipient sites were followed up.Results:Forty-five cases were performed in this study. There were 33 males and 12 females. The ages of the patients ranged from 21 to 65 years with an average of 35.2 years. The size of the defects ranged from 7 cm×6 cm to 32 cm×12 cm, with bone defects in 14 cases. The recipient sites included the free ALT flap in 17 (ranged from 11 cm×7 cm to 30 cm×12 cm), LDMF in 14 (ranged from 10 cm×7 cm to 32 cm×12 cm), ALT (ranged from 9 cm×6 cm to 16 cm×8 cm) + osteocutaneous fibula flap(ranged from 6 cm×4 cm to 9 cm×5 cm ) in 6, and iliac osteocutaneous flap based on SCIA (ranged from 7 cm×6 cm to 13 cm×8 cm). Among the 45 cases, 44 cases survived. There was one case with dorsal foot defect, which reconstructed by ALT flap, had vascular crisis after surgery. Although the vascular exploration was timely, the flap eventually necrotic. The ALT flap on the other side was successfully reapplied. Patients were followed up for average 4 years (ranging from 1-13 years), and all of them were satisfied with the function and final aesthetic outcomes. The two-point discrimination of the flap was 5 mm to 10 mm. The donor site healed well. There was no obvious scar hyperplasia except the latissimus dorsi donor.Conclusions:According to the size and depth of the large area of skin and soft tissue defects of extremities, and whether there are tendon, muscle and bone defects, a reasonable scheme is selected for repair, which can obtain good appearance and function after surgery, and less damage to the donor site.

Objective:This clinical study describes the surgical methods and clinical effects for large skin and soft tissue defects of the extremities.Methods:Between October 2005 and February 2019, the patients with large skin and soft tissue defects of the extremities were hospitalized in the Department of Hand Surgery of the Orthopedic Hospital of Taizhou. The choice of flaps for primary phase repair was determined by the degree and the type of defect, including anterolateral thigh (ALT) flap, latissimus dorsi myocutaneous flap (LDMF), combined free ALT flap and osteocutaneous fibula flap and vascularized iliac osteocutaneous flap based on superficial circumflex iliac artery (SCIA). The donor site was primarily closed. And the appearance and function of donor and recipient sites were followed up.Results:Forty-five cases were performed in this study. There were 33 males and 12 females. The ages of the patients ranged from 21 to 65 years with an average of 35.2 years. The size of the defects ranged from 7 cm×6 cm to 32 cm×12 cm, with bone defects in 14 cases. The recipient sites included the free ALT flap in 17 (ranged from 11 cm×7 cm to 30 cm×12 cm), LDMF in 14 (ranged from 10 cm×7 cm to 32 cm×12 cm), ALT (ranged from 9 cm×6 cm to 16 cm×8 cm) + osteocutaneous fibula flap(ranged from 6 cm×4 cm to 9 cm×5 cm ) in 6, and iliac osteocutaneous flap based on SCIA (ranged from 7 cm×6 cm to 13 cm×8 cm). Among the 45 cases, 44 cases survived. There was one case with dorsal foot defect, which reconstructed by ALT flap, had vascular crisis after surgery. Although the vascular exploration was timely, the flap eventually necrotic. The ALT flap on the other side was successfully reapplied. Patients were followed up for average 4 years (ranging from 1-13 years), and all of them were satisfied with the function and final aesthetic outcomes. The two-point discrimination of the flap was 5 mm to 10 mm. The donor site healed well. There was no obvious scar hyperplasia except the latissimus dorsi donor.Conclusions:According to the size and depth of the large area of skin and soft tissue defects of extremities, and whether there are tendon, muscle and bone defects, a reasonable scheme is selected for repair, which can obtain good appearance and function after surgery, and less damage to the donor site.

Objective To explore the clinical outcome of free chimeric anterolateral thigh cutaneotendinous flap with rectus femoris muscular flap for repairing the complex tissue defect of dorsum wrist. Methods From June, 2005 to March, 2014, free chimeric anterolateral thigh cutaneotendinous flap with rectus femoris muscular flap was used for repairing the complex tissue defect of dorsum wrist in 15 cases, which were 12 males and 3 females, and aged from 18 to 52 years old. The skin and soft tissue defect ranged from 8.0 cm×5.5 cm to 22.0 cm×12.0 cm. All ac-companied with extensor digitorum tendon loss. The tendon defect ranged from 5.0 cm to 12.0 cm (7.6 cm on average). The flap size ranged from 9.0 cm×6.5 cm to 23.0 cm×13.0 cm. The pedicle length ranged from 4.0 cm to 7.0 cm (5.3 cm on average). Results All flaps survived, and no postoperative complications occurred. The followed-up time ranged from 12 months to 36 months, and the texture of flap was flexible. No bulky was noted, and skin color was similar to the hand skin. The flexor and extensor function of wrist recovered satisfying. The 2-point discrimination of flap ranged from 9 mm to 15 mm (12.5 mm on average). Conclusion Free chimeric anterolateral thigh cutaneo-tendinous flap with rectus femoris muscular flap is a good option for repairing the complex tissue defect of dorsum wrist.

Objective To explore the clinical effects of calium dobesilate combined with compound thrombosis for patients with diabetic retinopathy due to visual field defect.Methods 112 cases of patients with diabetic retinopathy from February 2014 to February 2016 in our hospital were selected and randomly divided into the observation group and the control group,56 cases in each group.The control group were given compound Xueshuantong, while the observation group were treated with calcium dobesilate orally.And both the two groups were treated for five months.The hemangioma volume , macular thickness, hemorrhagic spot area, visual gray value, visual acuity, CRP, VEGF and IGF-1 levels in two groups were measured before and after treatment, as well as the clinical efficacy and adverse effects during the treatment.Results The total effective rate in the observation group was 94.6%significantly higher than that in the control group 71.4% (P<0.05).After treatment, in the two groups the hemangioma volume, macular thickness, hemorrhagic spot area, visual field gray value, visual acuity and 30°threshold sensitivity were significantly improved (P<0.05),but the improvement in the observation group was more (P<0.05).After treatment, the levels of hs-CRP, VEGF and IGF-1 were all significantly decreased (P<0.05), but the observation group decreased more significantly (P<0.05).Adverse reactions were mainly gastrointestinal reactions, and the incidence of adverse reactions in the two groups had no statistically significant difference.Couclusion Calcium dobesilate combined with compound thrombosis for patients with diabetic retinopathy due to visual field defect can improve the visual field defect of diabetic retinopathy patients.Its clinical effects is better and the safety is higher, which mechanism may be related to reducing the level of inflammatory factors in patients.