Li-Shu Wang

Pancreatic ductal adenocarcinoma cancer (PDAC) continues to pose a significant health burden, with a 5-year survival rate of only 10%. Prostate stem cell antigen (PSCA) is highly expressed on the surface of tumor cells of most PDAC patients, with minimum expression in most normal tissues. Here, we generated cryopreserved, off-the-shelf, allogeneic PSCA chimeric antigen receptor (CAR) invariant NKT (iNKT) cells using human peripheral blood mononuclear cells as a cell source. In multiple in vitro and in vivo PDAC models, freshly manufactured PSCA CAR_sIL-15 iNKT cells and frozen-thawed, off-the-shelf PSCA CAR_sIL-15 iNKT cells demonstrate comparable efficacies, and both show remarkable suppression of PSCA-positive and gemcitabine-resistant PDAC. Importantly, off-the-shelf cryopreserved PSCA CAR_sIL-15 iNKT cells show equivalent efficacy when compared with PSCA CAR T cells using the same PSCA CAR and in the same PDAC model; however, PSCA CAR_sIL-15 iNKT cells do not appear to induce systemic toxicity or graft-versus-host disease, thus allowing for multiple infusions to control recurrent disease. Collectively, our study suggests that PSCA CAR_sIL-15 iNKT cells merit clinical investigation for PDAC patients exhibiting positive PSCA expression. The therapy could be given as a single agent or in combination with established therapeutic modalities for PDAC.

Black raspberry (Rubus occidentalis) shows beneficial health effects, such as antioxidant, anti‐inflammatory, chemopreventive, antiproliferative, and antihyperglycemic activities. The present study investigated the antihyperglycemic activity of black raspberry extract (BRE) and potential mechanisms in skeletal muscle cells. Differentiated C2C12 myotubes were treated with the BRE (1–1000 μg/mL) or metformin (1 mM). The protein levels of various insulin signaling targets were measured by western blot analysis. BRE significantly increased glucose uptake by upregulated insulin receptor and phosphatidylinositol‐3 kinase (PI3K) in C2C12 cells, leading to enhanced translocation of glucose transporter 4 (GLUT4) to the plasma membrane. The expression of phosphorylated (p)‐adenosine monophosphate‐activated protein kinase (AMPK) was also enhanced by treatment with BRE, this resulting in stimulation of GLUT4 translocation to the plasma membrane and hence glucose uptake in skeletal muscles. These results suggest that BRE has an antihyperglycemic effect by stimulating GLUT4 translocation to the plasma membrane via activating the PI3K and AMPK pathways in skeletal muscle cells, thereby upregulating glucose uptake. Black raspberry is a potential functional food and has important implications for preventing and treating type‐2 diabetes. In addition, our study found that the flavonoids fraction is the main contributor fraction to promote glucose uptake in C2C12 cells.

Postbiotics is a novel category of biotics that encompasses dead cells, metabolites, and derivatives from gut microbiota. These substances can exhibit their effects without containing cells, such as in cell‐free supernatants and spent media. Examples of widely studied postbiotics include short‐chain fatty acids, exopolysaccharides, cell wall fragments, and bacterial lysates. Evidence suggests that postbiotics have numerous benefits for human health, including antiaging, and anti‐inflammatory properties, and participation in immune and lipid metabolism regulation. Specifically, postbiotics can improve intestinal health by strengthening the intestinal barrier, reducing inflammation, and promoting antibacterial activity. These findings may pave the way for the development of postbiotic functional foods in the future. This review provides an overview of the components, health effects, and industrial applications of postbiotics, aiming to consolidate existing research conclusions and serve as a reference for future studies.

The study was focused on the therapeutic potential of schaftoside (SS), a key bioactive compound found in Plumula nelumbinis, in the context of “Shanghuo,” an excessive internal heat condition induced by the overconsumption of capsaicin. “Shanghuo” in traditional Chinese medicine is characterized by symptoms like skin and mucous membrane redness, swelling, fever, and discomfort. It is commonly used to describe symptoms such as intense thirst, constipation, and a rapid or surging pulse. In modern medicine, it is associated with various factors, including dietary irritants, stress, gut microbiota imbalances, and immunological issues. The concept of Yin–Yang balance is pivotal in the theory of traditional Chinese medicine. Yin embodies elements of stability and inhibition, whereas Yang is indicative of vitality and assertiveness. Excessive capsaicin intake can also trigger “Shanghuo” symptoms by disrupting the body's balance of “Yin and Yang.” In the present study, we isolated SS from P. nelumbinis and performed in vitro antioxidant assays. SS exhibited a concentration‐dependent increase in antioxidant activity, indicating its potential to combat oxidative stress. In animal experiments, rats exposed to a high dose of capsaicin showed elevated levels of inflammatory markers and reduced antioxidant levels. SS effectively mitigated these imbalances, restored antioxidant enzyme activity, and reduced inflammation. Furthermore, capsaicin‐treated rats showed decreased energy metabolism and altered gut microbiota. SS treatment enhanced energy metabolism and increased the abundance of intestinal flora, highlighting its potential to restore metabolic balance. In conclusion, SS from P. nelumbinis shows promise in alleviating “Shanghuo” induced by excessive capsaicin intake.

In this paper, we explored the influence of lipase on cuticle wax and anthocyanin metabolism in blueberries. The results demonstrated a progressive alteration in wax crystal structure, transitions from rod‐like to short rod‐like and flaky, and even disappearance of the cuticle wax. Gas chromatography–mass spectrometry analysis revealed a reduction in esters, aldehydes, long‐chain alkanes, and total wax content following lipase treatment of blueberry fruits. Additionally, ultra high performance liquid chromatography–mass spectrometry analysis showed significant decreases in peonidin, petunidin, cyanidin, and delphinidin, accompanied by an increase in malvidin content due to lipase treatment. Subsequent investigations uncovered that lipase treatment inhibited the activities of key anthocyanin synthetic enzymes, namely phenylalanine ammonia‐lyase (PAL), chalcone isomerase (CHI), and dihydroflavonol reductase (DFR). Moreover, lipase treatment downregulated the expression of synthesis‐related genes, including PAL, 4‐coumarate: CoA ligase, chalcone synthase (CHS), CHI, and DFR. In summary, our findings indicate that lipase disrupts the integrity of cuticle wax structure, inhibits anthocyanin synthesis, and reduces anthocyanin content. Accordingly, our studies suggest that inhibiting lipase could offer a novel approach to preserving the freshness and anthocyanin concentration of blueberries.

Familial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, whereas the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry–based non‐targeted metabolomics, we analyzed pre‐ and post‐BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways, including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post‐BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.

Athena Dong, Yi-Wen Huang, Ben Niu, Ruiling Liu, Weijie Wu, Haiyan Gao, Jianhua Yu, Li-Shu Wang. J Cancer Prev 2023;28:212-8. https://doi.org/10.15430/JCP.2023.28.4.212