METHODS: C. nutans leaves was extracted with 50-100% ethanol or deionised water at 1% (w/v). Human umbilical veins endothelial cell (HUVEC) proliferation was examined using MTT assay. The in vitro anti-angiogenic effects of C. nutans were assessed using wound scratch, tube formation and transwell migration assays. The VEGF levels secreted by human oral squamous cell carcinoma (HSC-4) cell and HUVEC permeability were also measured. Besides, the rat aortic ring and chick embryo chorioallantoic membrane (CAM) assays, representing ex vivo and in vivo models, respectively, were performed.
RESULTS: The MTT assay revealed that water extract of C. nutans leaves exhibited the highest activity, compared to the ethanol extracts. Therefore, the water extract was chosen for subsequent experiments. C. nutans leaf extract significantly suppressed endothelial cell proliferation and migration in both absence and presence of VEGF. However, the water extract failed to suppress HUVEC transmigration, differentiation and permeability. C. nutans water extract also did not suppress HSC-4 cell-induced VEGF production. Importantly, C. nutans water extract significantly abolished the sprouting of vessels in aortic rings as well as in chick embryo CAM.
CONCLUSION: In conclusion, these findings reveal potential anti-angiogenic effects of C. nutans, providing new evidence for its potential application as an anti-angiogenic agent.
METHODS: The TCGA portal was employed in this investigation to find APOC1 expression in CRC. Its correlation with other genes and clinicopathological data was examined using the UALCAN database. To validate APOC1's cellular location, the Human Protein was employed. In order to forecast the relationship between APOC1 expression and prognosis in CRC patients, the Kaplan-Meier plotter database was used. TISIDB was also employed to evaluate the connection between immune responses and APOC1 expression in CRC. The interactions of APOC1 with other proteins were predicted using STRING. In order to understand the factors that contribute to liver metastasis from CRC, single-cell RNA sequencing (scRNA-seq) was done on one patient who had the disease. This procedure included sampling preoperative blood and the main colorectal cancer tissues, surrounding colorectal cancer normal tissues, liver metastatic cancer tissues, and normal liver tissues. Finally, an in vitro knockdown method was used to assess how APOC1 expression in tumor-associated macrophages (TAMs) affected CRC cancer cell growth and migration.
RESULTS: When compared to paracancerous tissues, APOC1 expression was considerably higher in CRC tissues. The clinicopathological stage and the prognosis of CRC patients had a positive correlation with APOC1 upregulation and a negative correlation, respectively. APOC1 proteins are mostly found in cell cytosols where they may interact with APOE, RAB42, and TREM2. APOC1 was also discovered to have a substantial relationship with immunoinhibitors (CD274, IDO1, and IL10) and immunostimulators (PVR, CD86, and ICOS). According to the results of scRNA-seq, we found that TAMs of CRC tissues had considerably more APOC1 than other cell groups. The proliferation and migration of CRC cells were impeded in vitro by APOC1 knockdown in TAMs.
CONCLUSION: Based on scRNA-seq research, the current study shows that APOC1 was overexpressed in TAMs from CRC tissues. By inhibiting APOC1 in TAMs, CRC progression was reduced in vitro, offering a new tactic and giving CRC patients fresh hope.
METHOD: A total of 36 Malaysian community-dwelling older adults with MCI (60-75-year-old) were randomized into Biokesum® (n = 18) and placebo group (n = 18). Each subject consumed one capsule of Biokesum® (250 mg/capsule) or placebo (maltodextrin, 280 mg/capsule) twice daily for 6 months. Cognitive function and mood were assessed at baseline, 3rd, and 6th-month using neuropsychological tests (MMSE, Digit Span, RAVLT, Digit Symbol, and Visual Reproduction) and Profile of Mood State (POMS) questionnaire. Blood lipid profile, fasting blood glucose, and biomarkers (MDA, LPO, COX-2, iNOS, and BDNF) were measured at baseline and 6th month. By the end of the intervention, there were 30 compliers (Biokesum®: N = 15; Placebo: N = 15) and 6 dropouts. For brain activation assessment, 15 subsamples (Biokesum®: N = 8; Placebo: N = 7) completed N-back and Stroop tasks during fMRI scanning at baseline and 6th month. The dorsolateral prefrontal cortex (Brodmann's area 9 and 46) was identified as a region of interest (ROI) for brain activation analysis using SPM software.
RESULTS: Two-way mixed ANOVA analysis showed significant improvements in Visual Reproduction II (p = 0.012, partial η2 = 0.470), tension (p = 0.042, partial η2 = 0.147), anger (p = 0.010, partial η2 = 0.207), confusion (p = 0.041, partial η2 = 0.148), total negative subscales (p = 0.043, partial η2 = 0.145), BDNF (p = 0.020, partial η2 = 0.179) and triglyceride (p = 0.029, partial η2 = 0.237) following 6 months of Biokesum® supplementation. Preliminary finding also demonstrated significant improvement at 0-back task-induced right DLPFC activation (p = 0.028, partial η2 = 0.652) among subsamples in Biokesum® group. No adverse events were reported at the end of the study.
CONCLUSION: Six months Biokesum® supplementation potentially improved visual memory, negative mood, BDNF, and triglyceride levels among older adults with MCI. Significant findings on brain activation at the right DPLFC must be considered as preliminary.
TRIAL REGISTRATION: Retrospectively registered on 30th August 2019 [ ISRC TN12417552 ].
OBJECTIVE: This study aimed to determine the relationship between dietary intake (macronutrients, fruits, vegetables and lycopene), lifetime physical activity and oxidative DNA damage with prostate cancer.
DESIGN: A case control study was carried out among 105 subjects (case n=35, control n=70), matched for age and ethnicity. Data on sociodemographic, medical, dietary intake, consumption of lycopene rich food and lifetime physical activity were obtained through an interview based questionnaire. Anthropometric measurements including weight, height and waist hip circumferences were also carried out on subjects. A total of 3 mL fasting venous blood was drawn to assess lymphocyte oxidative DNA damage using the alkaline comet assay.
RESULTS: Cases had a significantly higher intake of fat (27.7 ± 5.5%) as compared to controls (25.1 ± 5.9%) (p < 0.05). Mean intakes of fruits and vegetables (3.11 ± 1.01 servings/d)(p < 0.05), fruits (1.23 ± 0.59 servings/d) (p<0.05) and vegetables (1.97 ± 0.94 servings/d) were higher in controls than cases (2.53 ± 1.01, 0.91 ∓ 0.69, 1.62 ± 0.82 servings/d). A total of 71% of cases did not met the recommendation of a minimum of three servings of fruits and vegetables daily, as compared to 34% of controls (p < 0.05) (adjusted OR 6.52 (95% CI 2.3-17.8)) (p < 0.05). Estimated lycopene intake among cases (2,339 ∓ 1,312 mcg/d) were lower than controls (3881 ∓ 3120 mcg/d) (p< 0.01). Estimated lycopene intake of less than 2,498 mcg/day (50th percentile) increased risk of prostate cancer by double [Adjusted OR 2.5 (95%CI 0.99-6.31)]. Intake of tomatoes, watermelon, guava, pomelo, papaya, mango, oranges, dragon fruit, carrot, tomato sauce and barbeque sauce were higher in controls compared to cases. Intake of tomato sauce of more than 2.24 g/d (25th percentile), papaya more than 22.7 g/d (50th percentile) and oranges more than 19.1g/h (50th percentile) reduced prostate cancer risk by 7.4 (Adjusted OR 7.4 (95% CI 1.17-46.8)), 2.7 (adjusted OR 2.75 (95% CI 1.03-7.39)) and 2.6 times (adjusted OR = 2.6 (95% CI=1.01-6.67)), respectively (p < 0.05 for all parameters). No oxidative damage was observed among subjects. Past history of not engaging with any physical activities at the age of 45 to 54 years old increased risk of prostate cancer by approximately three folds (Adjusted OR 2.9(95% CI = 0.8-10.8)) (p < 0.05). In conclusion, low fat diet, high intake of fruits, vegetables and lycopene rich foods and being physical active at middle age were found to be protective. Thus, it is essential for Malaysian men to consume adequate fruits and vegetables, reduce fat intake and engage in physical activity in order to reduce prostate cancer risk.