Evaluation of Anti-Hyperglycemia and Complications of Red and Black Thai Jasmine Rice Cultivars in Streptozotocin-Induced Diabetic Rats

The phytochemical constituents of red (RR) and black (BR) rice extracts were determined using high-pressure liquid chromatography (HPLC). Phytochemical screening revealed the presence of catechin, rutin, isoquercetin, cyanidin 3-glucoside, cyanidin 3-O-rutinoside, peonidin and quercetin. The anti-diabetic activities of RR and BR extracts on diabetic complications were examined in a streptozotocin-induced diabetic rat model. Rats (n = 80) were divided into 10 groups (n = 8 rats per group). Healthy and diabetic RR or BR-treated groups received 10, 50, or 200 mg of RR or BR per kg of body weight daily for 45 days. The results demonstrated significantly improved glucose control in rats administered RR or BR, while triglyceride and cholesterol levels were reduced in the diabetic groups. Moreover, RR or BR treatment led to decreased levels of malondialdehyde, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine. Further, glutathione concentration was significantly increased in both serum and liver tissue from RR- and BR-treated diabetic rats

Inhibition of IL-10 and TGF-β receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells

Tumor escapes host immune responses by producing immunosuppressive cytokines, such as IL-10 and TGF-β, secreted into the tumor microenvironment. These cytokines play important roles in the suppression of dendritic cell (DC) function, leading to decreased immune responses of the effector CD4+ and CD8+ T cells. To improve DC functions and enhance cytolytic activity of activated effector T-cells, we suppressed the effect of these cytokines on DCs by using specific neutralizing antibodies that inhibit IL-10 and TGF-β receptors. Monocyte-derived DCs generated in vitro showed up-regulation of MHC (HLA-DR) and co-stimulatory molecules (CD40 and CD86). The IL-10 and TGF-β receptors were expressed and localized on cell membrane of DCs, as shown by Western blot analysis and immunofluorescence staining, whereas the IL-10 and TGF-β ligands were detected in the culture supernatants of DCs and cholangiocarcinoma (CCA) cell line, respectively. Inhibition of the IL-10 and TGF-β receptors on DCs by specific neutralizing antibodies significantly increased level of IFN-γ and enhanced cytolytic activity of the DC-activated effector T-cells against CCA cell line. These results indicate that the IL-10 and TGF-β receptors are the targets for inhibition to increase DC functions and enhance cytolytic activity of the DC-activated effector T-cells against CCA cells. Thus, inhibition of the IL-10 and TGF-β receptors on DCs is crucial in the preparation of DC-activated effector T cells for adoptive T-cell therapy

Suppression of TGF-β and IL-10 receptors on self-differentiated dendritic cells by short-hairpin RNAs enhanced activation of effector T-cells against cholangiocarcinoma cells

Cholangiocarcinoma (CCA) is an aggressive tumor that is associated with high rates of recurrence and mortality. This is due, in part, to the fact that CCA cells and their microenvironment secrete immunosuppressive cytokines, transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), that inhibit dendritic cell (DC) functions, which, in turn, results in the decreased anti-tumor activity of T-cells. We hypothesized that the TGF-β receptor and IL-10 blockade on dendritic cells would improve DC function, thereby allowing improved activation of T cells against CCA cells. To test our hypothesis, we generated self-differentiated DCs (SD-DCs) via transduction of human peripheral blood monocytes with lentivirus expressing IL-4 and GM-CSF. SD-DCs were transduced with a second lentivirus containing short-hairpin RNAs (shRNAs) to knock-down TGF-βRII and IL-10RA mRNAs. Immunoblot confirmed the reduced expression levels of TGF-β and IL-10 receptors in both SD-DCs that were transduced with a single and/or combination of lentiviruses containing shRNAs. SD-DCs were thereafter pulsed with tumor antigens extracted from CCA cell lines in an effort to activate DC function. MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86) on SD-DCs were upregulated to levels comparable to those on DCs generated by the conventional method. Suppression of TGF-β and IL-10 receptors on SD-DCs influenced the effector T-cells to produce IFN-γ, which enhanced their ability to kill CCA cells. The preparation of adoptive effector T-cells holds the potential of becoming a novel therapy for cellular immunotherapy in CCA

Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytochemical compound isolated from Xylopia pierrei Hance, a plant found in Thailand, as a novel therapeutic agent for TNBC. MTT and clonogenic assays showed that 7R-AMDL significantly reduced the survival of breast cancer cell lines, with a markedly potent effect on MDA-MB-231 cells. Flow cytometry showed that treating MDA-MB-231 cells with 7R-AMDL at the concentration of dose 8 µM significantly increased early and late apoptosis after 24 and 48 h compared to the control group (p < 0.0001). The highest tested 7R-AMDL dose upregulated the death receptors and their ligands, with extrinsic and intrinsic apoptosis pathways significantly activated via the caspase cascade, compared to the untreated group (p < 0.05). In addition, immunoblots showed decreased BCL2-like 1 (BCL2L1/Bcl-xL) expression (p < 0.0001). Furthermore, wound healing and Transwell assays showed that at a non-cytotoxic dose (≤4 µM), 7R-AMDL significantly inhibited the MDA-MB-231 cell migration and invasion. This reduction in cell migration was associated with decreased matrix metallopeptidase 9 (MMP-9) expression (p < 0.01) and nuclear factor kappa B (NF-κB) activation (p < 0.05). Altogether, 7R-AMDL has anti-cancer effects against TNBC and the potential to be further developed and evaluated for treating this disease