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Chronic pancreatitis is a progressive disease characterized by irreversible morphological changes to the pancreas, typically causing pain and permanent loss of function. It is a poorly understood disease with the pathogenesis remaining unclear. The authors' previous data demonstrated that the inhibition of Toll‑like receptor 4 (TLR4) using TLR4 antagonist kinase (TAK)‑242 attenuates taurocholate‑induced oxidative stress via the regulation of mitochondrial function in the pancreatic acinar cells of mice. In the present study, the effect of TAK‑242 on trinitrobenzene sulfonic acid (TNBS)‑induced chronic pancreatitis was investigated in rats. The results revealed that TAK‑242 attenuated the severity of chronic pancreatic injury, and regulated extracellular matrix secretion and cellular immunity. In addition, TAK‑242 treatment significantly decreased cell apoptosis, as evidenced by the reduction in Terminal deoxynucleotidyl transferase dUTP nick end labeling‑positive cells in pancreas tissue sections, and also promoted cell proliferation in TNBS‑treated animals. Furthermore, the results of the calibrated von Frey filament assay demonstrated that TAK‑242 could prevent the pancreatitis‑induced referred abdominal hypersensitivity. In summary, TAK‑242 exhibits protective effects against TNBS‑induced chronic pancreatitis and may be a potential therapeutic strategy for the treatment of patients with chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Gossypol is a polyphenolic, yellowish compound derived from cottonseed extract. The present study examined the effects of gossypol on the apoptosis and autophagy of HT-29 cells. A Cell Counting Kit-8 assay, Annexin V-FITC, JC-1 staining and western blotting were used to identify the viability of cells, stages of apoptosis and the expression levels of the signaling proteins. Gossypol promoted apoptosis and induced the loss of mitochondrial membrane potential. Further investigation of the apoptotic mechanism revealed that gossypol increased the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 protein levels and upregulated the expression of caspase-3. Gossypol also enhanced the activity of microtubule-associated protein light chain 3 LC3-II and Beclin-1 and downregulated LC3-I, in a dose-dependent manner. Together, these finding suggested that gossypol may be a novel and potential antitumor agent. [ABSTRACT FROM AUTHOR]

The cysteine protease cathepsin B (Cat B) is important in the progression of tumor cells, however, the function and molecular mechanisms of Cat B in hepatocellular carcinoma (HCC) remain to be elucidated. Our previous study demonstrated that integrin αvβ3 regulated the biological behavior of HCC. The present study demonstrated that Cat B was also important in cell proliferation and apoptosis in HCC. Notably, Cat B was observed to activate the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway to promote HCC proliferation. Furthermore, inhibition of integrin αvβ3 significantly prevented Cat B-induced activation of PI3K/Akt and the progression of HCC. Thus, the results of the present study suggested the presence of a Cat B/integrin αvβ3/PI3K/Akt axis in the regulation of the progression of HCC. [ABSTRACT FROM AUTHOR]