Upregulation of APAF1 and CSF1R in Peripheral Blood Mononuclear Cells of Parkinson’s Disease

Increased oxidative stress and neuroinflammation play a crucial role in the pathogenesis of Parkinson’s disease (PD). In this study, the expression levels of 52 genes related to oxidative stress and inflammation were measured in peripheral blood mononuclear cells of the discovery cohort including 48 PD patients and 25 healthy controls. Four genes, including ALDH1A, APAF1, CR1, and CSF1R, were found to be upregulated in PD patients. The expression patterns of these genes were validated in a second cohort of 101 PD patients and 61 healthy controls. The results confirmed the upregulation of APAF1 (PD: 0.34 ± 0.18, control: 0.26 ± 0.11, p CSF1R (PD: 0.38 ± 0.12, control: 0.33 ± 0.10, p = 0.005) in PD patients. The expression level of APAF1 was correlated with the scores of the Unified Parkinson’s Disease Rating Scale (UPDRS, r = 0.235, p = 0.018) and 39-item PD questionnaire (PDQ-39, r = 0.250, p = 0.012). The expression level of CSF1R was negatively correlated with the scores of the mini-mental status examination (MMSE, r = −0.200, p = 0.047) and Montréal Cognitive Assessment (MoCA, r = −0.226, p = 0.023). These results highly suggest that oxidative stress biomarkers in peripheral blood may be useful in monitoring the progression of motor disabilities and cognitive decline in PD patients

Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems.

Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa

Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems.

Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa

Resveratrol (RV) and peanut stem extract (PSE) enhance irradiation (IR)-induces double-strand breaks (DSBs) in radioresistant prostate cancer cells.

<p>Protein expression levels of target molecules in LAPC4-KD cells that were untreated (mock), exposed to IR (2Gy) alone, or in combination with RV or PSE (25 or 500 μg/mL, respectively). Representative western blot results from one of three independent experiments are shown. β-actin was the loading control. Expression level of each protein was quantified using signal intensity and indicated below each lane.</p

Resveratrol (RV) and peanut stem extract (PSE) significantly enhance irradiation (IR)-suppression of prostate cancer growth <i>in vivo</i>.

<p>(A) Mice with xenograft tumors were divided into four groups and were treated with vehicle (mock, control) or IR alone or combined with RV or PSE (5 or 250 mg/kg, respectively). Arrows indicated tumor that was grown in the posterior flanks of mice. (B) Treatments were administered on day 0, 3, 7, and 14. After euthanasia, tumors were excised from mice. Scales shown in images are in centimeter. (C) Tumor volume was calculated, and data are means ± standard deviations; *, <i>P</i> < 0.01 compared to each group.</p

Resveratrol (RV) and peanut stem extract (PSE) increase radiosensitivity of prostate cancer cells.

<p>LAPC4-KD cells were treated with irradiation (IR, 0–6 Gy) alone or combined with RV or PSE (25 or 500 μg/mL, respectively). After 10-day incubation, survival cell colonies were (A) stained with crystal violet and (B) assessed using clonogenic assays as described in the methods section.</p

Resveratrol (RV) and peanut stem extract (PSE) inhibit proliferation of radioresistant prostate cancer.

<p>(A) LAPC4-KD were treated with RV or PSE at indicated concentrations (0–1000 μg/mL) for 48 h. (B) LAPC4-KD and PC3-KD cells were treated with RV or PSE (25 or 500 μg/mL, respectively) for 48 h. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. Statistical significance was evaluated using Student’s <i>t</i>-test (*, <i>P</i> < 0.01).</p