Lemuteporfin

The tissue inhibitor of metalloproteinase 2 (TIMP2), a natural inhibitor of matrix metalloproteinase (MMP), regulates inflammation, fibrosis, and cell proliferation. Chronic renal allograft dysfunction (CRAD) is a primary factor affecting the long-term survival of renal allografts. We assessed whether up-regulation of TIMP2 expression may affect the ERK1/2-NF-κB signaling pathway and CRAD development.

Lewis rats received orthotopic F344 kidney allografts to establish the classical CRAD model. The treatment group was injected with a lentivirus encoding a TIMP2-targeting small hairpin (sh)RNA (LTS) at 5 × 10⁸ TU/ml monthly after kidney transplantation. A second CRAD group was injected with a lentivirus TIMP2-control vector (LTC). After 12 weeks, blood, urine, and kidney tissue were harvested to evaluate renal function and pathological examinations. Hematoxylin and eosin staining, Masson staining, and Periodic acid-Schiff staining were performed for renal histopathological evaluation according to the Banff criteria. TIMP2, phospho (p)-ERK1/2, p-p65 (NF-κB) expression levels were measured via immunohistochemical and Western blot analyses.

Compared to the F344 and Lewis control groups, the expression of TIMP2, p-ERK1/2, and p-p65 were significantly higher in the CRAD and CRAD+LTC renal tissues (p < 0.05). There were also increased levels of serum creatinine, nitrogen, and 24 h urinary protein in these two groups (p < 0.05). Typical histopathological changes of CRAD were observed in the CRAD and CRAD+LTC groups. Administration of LTS effectively decreased the expression of TIMP2, p-ERK1/2, and p-P65, and reduced interstitial fibrosis and macrophage infiltration in the treatment group (p < 0.05). Additionally, MCP1 and ICAM-1, which are downstream cytokines of the NF-κB pathway, were also inhibited in the renal rat kidney from the LTS group (p < 0.05). Furthermore, renal function was well preserved in the LTS group compared to the CRAD group and CRAD+LTC group.

A decrease of TIMP2 can alleviate the progression of inflammation in CRAD via inhibition of the ERK1/2-NF-κB signaling pathway.

A study was conducted to evaluate the efficiency of guanidinoacetic acid (GAA) in diets containing varying levels of corn replacement with low-tannin sorghum (LTS) for laying hens in the later stage of production. In a 12-wk study, a total of 288 laying hens at 52 wk of age were divided into 6 treatment groups. Each treatment group had 8 replicates, each of which consisted of 6 hens. A 2 × 3 factorial design was used to investigate the impact of substituting corn with LTS at 3 levels (100% corn, 50% LTS, and 100% LTS) with 2 doses of GAA supplementation (0 and 0.6 g/kg). The results indicate that there were interaction effects (P < 0.05) between diet type and GAA supplementation on protein digestibility and AMEn, with the GAA supplement being more effective in the 100% LTS group. Replacing corn with LTS at both levels had no negative effects on performance and metabolic profile. In contrast, the 100% LTS diet increased monounsaturated fatty acids in the yolk (P < 0.05), but decreased the yolk color index, the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA) in the yolk, ileal digestibility of energy, and AMEn when compared to the 100% corn diet (P < 0.05). Regardless of the diet, dietary supplementation with GAA resulted in increases (P < 0.05) in shell-breaking strength, the PUFA to SFA ratio in egg yolk, and concentrations of creatine and nitric oxide in serum. There was also a decrease (P < 0.05) in serum malondialdehyde concentration with GAA supplementation. In conclusion, the positive effects of GAA on protein digestibility and AMEn were found to be more pronounced when corn was completely replaced with LTS. However, the positive effects of GAA on egg-laying performance, eggshell quality, antioxidant status, and yolk fatty acid composition remained consistent regardless of the extent to which corn was substituted with LTS.