Sergenex Co. Ltd.

Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis.

Upon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models.

In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker).

These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Background: Postoperative pancreatic fistula (POPF) is a significant complication following pancreatic surgery, considerably influenced by the texture of the pancreatic tissue. This study aims to explore the potential of Penicillin G (PG) in reducing the severity of POPF in a porcine surgical model. Study Design: After performing distal pancreatectomy with pancreaticojejunostomy (PJ), pigs were administered either normal saline or varying concentrations of PG (0.75, 1.5, and 3.0 mM) at the PJ site. The study estimated POPF by measuring pancreatic hardness, tensile force, fibrosis, and amylase levels in Jackson-Pratt (JP) drain samples. Results: Intraparenchymal PG injection significantly increased pancreatic hardness and tensile force (p < 0.05) while upregulating profibrotic markers like MMP2 and TGF-β1, indicating enhanced fibrosis (p < 0.05). Importantly, these profibrotic changes reverted to baseline levels by POD 14, suggesting reversible fibrosis without lasting consequences. The 0.75 PG and 1.5 PG groups exhibited significantly lower JP amylase levels than the control group on both POD 3 and POD 4 (p < 0.05). Notably, the 0.75 PG group also demonstrated the highest survival rate compared to the 1.5 PG and NS groups (p < 0.05). Conclusions: The intrapancreatic PG injection could effectively reduce the severity of POPF by promoting wound healing through intensified fibrosis around the PJ site.

By inhibiting the conversion of lysophosphatidylcholine into lysophosphatidic acid, a process pivotal to tumor progression, the autotaxin (ATX) inhibitor PF-8380 offers a new anticancer therapeutic strategy, distinct from the action mechanism of sorafenib. This study explored the potential anticancer effects of the PF-8380 on hepatocellular carcinoma (HCC) cells, especially sorafenib-resistant strains. The investigation included both in vitro and in vivo experiments to evaluate the impact of PF-8380 treatment on epithelial-mesenchymal transition (EMT) and autophagy markers. An orthotopic HCC model served as the in vivo platform. PF-8380 showed a significant reduction in cell viability in both sorafenib-susceptible and resistant HCC cells. It effectively altered EMT by increasing E-cadherin and reducing Snail levels, and inhibited autophagy, as indicated by changes in LC3 and p62 markers. These effects were consistently observed in the orthotopic HCC mouse model, reinforcing PF-8380’s potential as a dual inhibitor of EMT and autophagy in HCC treatment. Our research indicates that PF-8380 could provide substantial therapeutic benefits in the treatment of HCC, even in cases resistant to sorafenib, primarily by suppressing both EMT and autophagy processes.