A task-specific cognitive domain decline is correlated with plasma and neuroimaging markers in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a disabling non-motor symptom of Parkinson's disease (PD). It remains uncertain whether declines in specific cognitive domains relate to imaging or plasma biomarkers across the disease continuum. OBJECTIVE: We investigated whether neuroimaging and plasma biomarkers correlate with individual task-specific cognitive domain declines evidenced by computerized neuropsychological tests in PD patients. METHODS: A total of 107 participants, including 87 PD patients (30 with normal cognition [PD-NC], 30 with mild cognitive impairment [PD-MCI], 27 with dementia [PDD]), and 20 healthy controls, were recruited. All received the Cambridge Neuropsychological Test Automatic Battery (CANTAB) test, brain MRI, and assays of plasma biomarkers, including α-synuclein, tau, Aß42, and Aß40. RESULTS: PD patients had generally poorer cognitive performance than controls. Patients with PD-MCI and PDD had worse performance in visual, verbal, and working memory and executive function than those with PD-NC. After adjusting for covariates, PDD patients had global cortical thinning, especially in the temporal and parietal lobes, and higher plasma α-synuclein levels and tau:Aß42 ratios than PD-NC group. Plasma α-synuclein level was associated with frontal lobe-mediated tasks, while the tau:Aß42 ratio was associated with posterior cortical-mediated tasks. Facial emotion recognition tasks and visual pattern recognition associated with frontotemporal cortical thinning. The accuracy of predicting PDD using age alone (area under the curve [AUC] 0.756) increased by incorporating plasma biomarkers (AUC = 0.851, p = 0.025). CONCLUSIONS: Cognitive decline in PD patients has a task-specific correlation with neuroimaging and plasma biomarkers, which may implicate the underlying neuropathological process of PDD.

An integrated biometric voice and facial features for early detection of Parkinson's disease.

Hypomimia and voice changes are soft signs preceding classical motor disability in patients with Parkinson's disease (PD). We aim to investigate whether an analysis of acoustic and facial expressions with machine-learning algorithms assist early identification of patients with PD. We recruited 371 participants, including a training cohort (112 PD patients during "on" phase, 111 controls) and a validation cohort (74 PD patients during "off" phase, 74 controls). All participants underwent a smartphone-based, simultaneous recording of voice and facial expressions, while reading an article. Nine different machine learning classifiers were applied. We observed that integrated facial and voice features could discriminate early-stage PD patients from controls with an area under the receiver operating characteristic (AUROC) diagnostic value of 0.85. In the validation cohort, the optimal diagnostic value (0.90) maintained. We concluded that integrated biometric features of voice and facial expressions could assist the identification of early-stage PD patients from aged controls.

Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death.

PURPOSE: Radiotherapy is the most efficacious strategies for lung cancer. The radiation-enhancing effects and the underlying mechanisms of berberine were investigated both in vitro and in vivo. METHODS AND MATERIALS: Clonogenic survival assays were used to evaluate the radio-sensitivity of berberine on non-small-cell lung cancer. Electron microscopic observation of the features of cell death, flow cytometry of acidic vascular organelles formation, mitochondria membrane potential and cell-cycle progression, and Western blotting of caspase 3, PARP, and LC3 were performed to identify the mechanisms underlying the enhancing effects. Lewis lung carcinoma model in mice was conducted to evaluate the possible application of berberine in synergistic treatment with irradiation. RESULTS: Compared with radiation alone (SF2 = 0.423; D(0) = 5.29 Gy), berberine at 5 and 10 muM concentrations in combination with radiation showed significant enhancement on radiation-induced clonogenic inhibition (SF2 = 0.215: D(0) = 2.70 Gy and SF2 = 0.099: D(0) = 1.24 Gy) on A549 cells. The cellular ultrastructure showed the presence of autophagosome and an increased proportion of acridine orange stain-positive cells, demonstrating that berberine enhanced radiosensitivity via autophagy. The process involved LC3 modification and mitochondrial disruption. The animal model verified the synergistic cytotoxic effect of berberine and irradiation resulting in a substantial shrinkage of tumor volume. CONCLUSION: Supplement of berberine enhanced the cytotoxicity of radiation in both in vivo and in vitro models of lung cancer. The mechanisms underlying this synergistic effect involved the induction of autophagy. It suggests that berberine could be used as adjuvant therapy to treat lung cancer.

Induction of autophagy and apoptosis by the extract of Solanum nigrum Linn in HepG2 cells.

Solanum nigrum L. (SN) has been used in traditional folk medicine to treat different cancers. It is also used as a hepatoprotective and anti-inflammatory agent. In this study, we demonstrated that the extract of SN (SNE) induced a strong cytotoxic effect toward HepG2 cells but much less to Chang liver and WRL-68 cells. The mechanisms of the cytotoxic effect were concentration-dependent. High doses of SNE (2 and 5 mg/mL) induced apoptotic cell death in HepG2 cells, as evidenced by increases in the expressions of p-JNK and Bax, mitochodrial release of cytochrome c, and caspase activation. On the other hand, cells treated with low concentrations of SNE (50-1000 microg/mL) revealed morphological and ultrastructural changes of autophagocytic death under electron microscopic observation. Furthermore, these cells showed increased levels of autophagic vacuoles and LC3-I and LC3-II proteins, specific markers of autophagy. The levels of Bcl-2 and Akt that have been implicated in the down-regulation of autophagy were decreased upon SNE treatment. Taken together, these findings indicate that SNE induced cell death in hepatoma cells via two distinct antineoplastic activities of SNE, the ability to induce apoptosis and autophagocytosis, therefore suggesting that it may provide leverage to treat liver cancer.

Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats.

Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.

Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2.

Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-kappaB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.