The Role of Curcumin in Cancer Treatment.

Curcumin is a polyphenol extracted from the rhizomes of the turmeric plant, Curcuma longa which has anti-inflammatory, and anticancer properties. Chronic inflammation is associated with the development of cancer. Curcumin acts on the regulation of various immune modulators, including cytokines, cyclooxygenase-2 (COX-2), and reactive oxygen species (ROS), which partly explains its anticancer effects. It also takes part in the downregulation of growth factors, protein kinases, oncogenic molecules and various signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (STAT3) signaling. Clinical trials of curcumin have been completed or are ongoing for various types of cancer. This review presents the molecular mechanisms of curcumin in different types of cancer and the evidence from the most recent clinical trials.

Expression of orexin-A (hypocretin-A) in the hypothalamus after traumatic brain injury: A postmortem evaluation.

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity. The key component of TBI pathophysiology is traumatic axonal injury (TAI), commonly referred to as diffuse axonal injury (DAI). Coma is a serious complication which can occur following traumatic brain injury (TBI). Recently, studies have shown that the central orexinergic/ hypocretinergic system exhibit prominent arousal promoting actions. Therefore, the purpose of this study is to investigate by immunohistochemistry the expression of beta-amyloid precursor protein (ß-APP) in white matter of parasagittal region, corpus callosum and brainstem and the expression of orexin-A (ORXA) in the hypothalamus after traumatic brain injury. RESULTS: DAI was found in 26 (53.06%) cases, assessed with ß-APP immunohistochemical staining in parasagittal white matter, corpus callosum and brainstem. Orexin-A immunoreactivity in hypothalamus was completely absent in 5 (10.2%) of the cases; moderate reduction of ORXA was observed in 9 (18.4%) of the cases; and severe reduction was observed in 7 (14.3%) of the cases. A statistically significant correlation was found between ß-APP immunostaining in white matter, corpus callosum and brainstem in relation to survival time (p < 0.002, p < 0.003 and p < 0.005 respectively). A statistically positive correlation was noted between ORX-A immunoreactivity in hypothalamus to survival time (p < 0.003). An inverse correlation was noted between the expression of ß-APP in the regions of brain studied to the expression of ORX-A in the hypothalamus of the cases studied (p < 0.005). CONCLUSIONS: The present study demonstrated by immunohistochemistry that reduction of orexin-A neurons in the hypothalamus, involved in coma status and arousal, enhanced the immunoexpression of ß-APP in parasagital white matter, corpus callosum and brainstem.

Transcutaneous Vagus Nerve Stimulation (t-VNS) and epilepsy: A systematic review of the literature.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (t-VNS) has been proposed as an alternative method for the treatment of various neurological and psychiatric disorders. Contrary to the classic invasive vagus nerve stimulation (i-VNS), t-VNS does not require surgical intervention. The application of t-VNS for the treatment of epilepsy has been poorly studied. Hence, we performed a systematic review of the literature to elucidate efficacy, adverse effects and technical features of t-VNS in patients with epilepsy. MATERIAL AND METHODS: We systematically searched MEDLINE and SCOPUS databases using the following keywords: [TRANSCUTANEOUS VAGUS NERVE STIMULATION OR TRANSCUTANEOUS VAGAL NERVE STIMULATION] AND [EPILEPSY OR SEIZURES]. We searched for observational studies in English concerning the application of t-VNS for the treatment of epilepsy in humans. The full-text version of relevant studies was obtained and reviewed. Technical parameters of the stimulation, percentage of seizure frequency reduction, QOLIE-31(Quality of Life In Epilepsy-31) and LSSS (Liverpool Seizure Severity Scale) questionnaires and adverse effects were recorded and analyzed. RESULTS: A total of 10 studies with 350 patients were included. Both bilateral and unilateral placement of the electrode were applied. Stimulation frequency varied from 10-30Hz, while treatment intensity was usually adjusted according to patients' preferences and tolerance (around 1mA) and below the pain threshold. In the clinical trials included in our review, the mean seizure frequency reduction varied from 30 to 65%. Eight and four studies provided information about QOLIE-31 and LSSS questionnaires respectively. Three studies reported a statistically significant (p<0,05) improvement in patients' quality of life and two studies reported statistically significant (p<0,05) seizure severity reduction. The most common side effect was headache (8,9%), followed by skin irritation at the placement site (7,1%) and nasopharyngitis (5,1%). No serious or life-threatening side effects were reported. CONCLUSION: Due to the heterogeneity of the included studies, no safe conclusions could be extracted concerning the efficacy of t-VNS. However, the results of this review suggest that patients with epilepsy could possibly benefit from the use of t-VNS. The present study also emphasizes the limitations of previous clinical trials concerning the applications of t-VNS in people with epilepsy and thus could be a guidance for the conduction of future trials.