effect-mechanism-tauroursodeoxycholic-acid-blue-fox-bile-on-acute

Effect and Mechanism of Tauroursodeoxycholic Acid in Blue Fox Bile on Acute Alcohol-Associated Liver Injury in Mice

Animal bile, such as bear bile, have long been used in traditional medicine for its therapeutic benefits. Blue fox bile, similar to bear bile, is believed ...

Heilongjiang University of Chinese Medicine

Lunasin is a naturally existing bioactive peptide with an Arg-Gly-Asp (RGD) motif, which competes with integrins to bind with the extracellular matrix (ECM) consequently suppressing the integrin-mediated signaling pathway. Owing to the RGD motif, lunasin has been proven as an effective anti-inflammatory, antitumor and antimetastatic agent in many types of cancer. However, knowledge of its inhibitory effect on metastasis and the related mechanism of action in breast cancer cells is limited. In this study, the inhibitory effect of lunasin on the proliferation, migration and invasion of two typical breast cancer cell lines, ER-negative MDA-MB-231 with αVβ3 expression and ER-positive MCF-7 with αVβ5/α5β1 expression, were examined in vitro as well the related mechanisms. The results demonstrated that lunasin (10-20 µM) effectively inhibited the migration and invasion activity and expression of matrix metalloproteinase (MMP)‑2/-9 in both breast cancer cell lines. Meanwhile, we also found that lunasin inhibited the phosphorylation of focal adhesion kinase (FAK), Src, Akt, ERK and nucleus translocation of NF-κB, which indicates that, possibly via competing with αVβ3 or αVβ5/α5β1 integrin, lunasin suppresses the metastasis of breast cancer cells through integrin-mediated FAK/Akt/ERK and NF-κB signaling pathways followed by downregulation of the activity and expression of MMP-2/-9.

Lunasin suppresses the migration and invasion of breast cancer cells by inhibiting matrix metalloproteinase-2/-9 via the FAK/Akt/ERK and NF-κB signaling pathways.

Hepatic ischemia-reperfusion (I-R) injury causes acute organ damage or dysfunction, and remains a problem for liver transplantation. In the I-R phase, the generation of reactive oxygen species aggravates the injury. In the current study, a novel selenocysteine-containing 7‑mer peptide (H-Arg-Sec-Gly-Arg-Asn-Ala-Gln-OH) was constructed to imitate the active site of an antioxidant enzyme, glutathione peroxidase (GPX). The 7‑mer peptide which has a lower molecular weight, and improved water‑solubility, higher stability and improved cell membrane permeability compared with other GPX mimics. Its GPX activity reached 13 U/µmol, which was 13 times that of ebselen (a representative GPX mimic). The effect of this GPX mimic on I‑R injury of the liver was assessed in rats. The 7‑mer peptide significantly inhibited the increase in serum hepatic amino‑transferases, tissue malondialdehyde, nitric oxide contents, myeloperoxidase activity and decrease of GPX activity compared with I‑R tissue. Following treatment with the 7‑mer peptide, the expression of B‑cell CLL/lymphoma‑2 (Bcl‑2) was significantly upregulated at the mRNA and protein level compared with the I‑R group, as determined by reverse transcription‑polymerase chain reaction and immunohistochemistry, respectively. By contrast, Bcl‑2 associated X protein (Bax) was downregulated by the 7‑mer peptide compared the I‑R group. Histological and ultrastructural changes of the rat liver tissue were also compared among the experimental groups. The results of the current study suggest that the 7‑mer peptide protected the liver against hepatic I‑R injury via suppression of oxygen‑derived free radicals and regulation of Bcl‑2 and Bax expression, which are involved in the apoptosis of liver cells. The findings of the present study will further the investigation of the 7-mer peptide as an effective therapeutic agent in hepatic I-R injury.

Protection of rat liver against hepatic ischemia-reperfusion injury by a novel selenocysteine-containing 7-mer peptide.

The incidence of colorectal cancer (CRC) poses a significant threat to human life. Immunotherapy has emerged as an efficacious treatment against CRC. However, it is hindered by the challenge of inadequate immunogenicity. In addition to exerting inhibitory effects on cancer cell activity, the chemotherapeutic agent oxaliplatin (OXP) possesses the advantage of inducing immunogenic cell death (ICD) through reactive oxygen species (ROS). Schisandrin A (SCHA) can augment ROS production stimulated by OXP in cancer cells and enhance the efficacy of ICD. Consequently, we developed a liposome formulation named FOS-lip that co-delivers SCHA and OXP to actively target CRC cells. The FOS-lip exhibited appropriate particle size, high drug loading capacity, and less than 5% hemolysis. Due to the pH sensitivity, both drugs were rapidly released under acidic conditions, providing a foundation for their therapeutic action. Furthermore, liposomes modified with active targeting moieties facilitated efficient internalization of drugs into cells. Through liposomal delivery, these two drugs synergistically inhibited tumor cells (CI < 1). FOS-lip significantly elevated ROS levels in tumor cells and importantly promoted the induction of ICD, leading to release/exposure of damage-associated molecular patterns (DAMPs) and enhanced dendritic cell maturation. Therefore, this study presents a strategy to enhance the immunogenicity of CRC by addressing the issue of insufficient OXP-induced ICD and offers valuable insights for future research.

Article	Year
Lunasin suppresses the migration and invasion of breast cancer cells by inhibiting matrix metalloproteinase-2/-9 via the FAK/Akt/ERK and NF-κB signaling pathways. Oncology reports\| PubMed ID: 27175819	2016
Protection of rat liver against hepatic ischemia-reperfusion injury by a novel selenocysteine-containing 7-mer peptide. Molecular medicine reports\| PubMed ID: 27431272	2016
Folate-modified liposomes for co-delivery of schisandrin A and oxaliplatin to enhance colorectal cancer cell death. Discover oncology\| PubMed ID: 40864196	2025

Qianqian Jiang

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