Recent Advances in Small Peptides of Marine Origin in Cancer Therapy.

Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. This paper highlights the anticancer linear and cyclic small peptides in marine resources and presents a review of peptides and the derivatives and their mechanisms.

Blood Pressure Variability during Angiography in Patients with Ischemic Stroke and Intracranial Artery Stenosis.

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.

The Posterior Insula Shows Disrupted Brain Functional Connectivity in Female Migraineurs Without Aura Based on Brainnetome Atlas.

Long-term headache attacks may cause human brain network reorganization in patients with migraine. In the current study, we calculated the topologic properties of functional networks based on the Brainnetome atlas using graph theory analysis in 29 female migraineurs without aura (MWoA) and in 29 female age-matched healthy controls. Compared with controls, female MWoA exhibited that the network properties altered, and the nodal centralities decreased/increased in some brain areas. In particular, the right posterior insula and the left medial superior occipital gyrus of patients exhibited significantly decreased nodal centrality compared with healthy controls. Furthermore, female MWoA exhibited a disrupted functional network, and notably, the two sub-regions of the right posterior insula exhibited decreased functional connectivity with many other brain regions. The topological metrics of functional networks in female MWoA included alterations in the nodal centrality of brain regions and disrupted connections between pair regions primarily involved in the discrimination of sensory features of pain, pain modulation or processing and sensory integration processing. In addition, the posterior insula decreased the nodal centrality, and exhibited disrupted connectivity with many other brain areas in female migraineurs, which suggests that the posterior insula plays an important role in female migraine pathology.

The sensorimotor network dysfunction in migraineurs without aura: a resting-state fMRI study.

Migraine is a common recurrent neurological disorder combining nausea, vomiting, and hypersensitivities to visual, auditory, olfactory and somatosensory stimuli. However, the dysfunction of the sensorimotor network in migraineurs has not been well clarified. In the present study, we evaluated the dysfunction of the sensorimotor network in 30 migraineurs without aura and in 31 controls by combining regional homogeneity (ReHo), amplitudes of low-frequency fluctuation (ALFF) and degree centrality (DC) analysis methods based on resting-state fMRI. A seed-based functional connectivity (FC) analysis was used to investigate whether the dysfunctional areas within the sensorimotor network exhibited abnormal FC with other brain areas. Compared to the controls, the migraineurs without aura exhibited significantly smaller ReHo, ALFF and DC values in the primary somatosensory cortex (S1) and right premotor cortex (PMC). The migraineurs showed weaker FC between the S1 and brain areas within the pain intensity and spatial discrimination pathways and trigemino-thalamo-cortical nociceptive pathway. We proposed that the dysfunction of the S1 and PMC and the decreased FC between the S1 and brain areas in migraineurs without aura may disrupt the discrimination of sensory features of pain and affect nociception pathways, and would be involved in the dysfunctional mechanism in migraine.

Predictive role of CHADS2 and CHA2DS2-VASc scores on stroke and thromboembolism in patients without atrial fibrillation: a meta-analysis.

OBJECTIVE: CHA2DS2-VASc is the extension of the CHADS2 score developed by Birmingham 2009. This risk stratification schema is often used in clinical setting when considering additional risk factors for developing stroke in AF patients. However, its role in the non-AF population is unknown. This study was designed to evaluate the accuracy of the CHADS2 and the CHA2DS2-VASc scoring systems. METHODS: Studies designed for CHADS2 and CHA2DS2-VASc score in stratifying the risks for stroke development in non-AF patients were included. RESULTS: Among the 114 studies identified, six trials were chosen finally and included for meta-analysis. The pooled diagnostic odds ratio (DOR) for CHADS2 and CHA2DS2-VASc was 2.86 (95% CI =1.83-4.28) and 2.80 (95% CI =1.83-4.28), respectively. CHA2DS2-VASc score was of better sensitivity than CHADS2 score (0.920 vs. 0.768). However, both scores were showed to have inherent heterogeneity and poor specificity. CONCLUSIONS: Though having good diagnostic accuracy, the clinical application of the CHADS2 and CHA2DS2-VASc scores in predicting risk of stroke development in non-AF patients still needs further validation. Key message The overall diagnostic accuracy of CHADS2 and CHA2DS2-VASc in stroke-risk stratification was good in patients with non-atrial fibrillation.

Pulse pressure as an independent predictor of stroke: a systematic review and a meta-analysis.

BACKGROUND: Recent evidence suggests that pulse pressure (PP) is a strong cardiovascular diseases' risk factor. We systematically evaluated all relevant studies to determine whether PP can be used as an independent predictor of stroke and mortality. METHODS AND RESULTS: A meta-analysis was performed by searching the published literature using MEDLINE, Cochrane and Google Scholar databases up to December 15, 2015. We measured the effect size expressed by hazard ratio (HR) and 95 % confidence interval (95 % CI). Eleven publications were included in the analysis. Pooled results demonstrated that 10 mmHg increase in PP was associated with increased risk of stroke occurrence (pooled HR 1.046, 95 % CI 1.025-1.068, P < 0.001). Additionally, systolic blood pressure (SBP) (pooled HR 1.053, 95 % CI 1.033-1.073, P < 0.001) and diastolic blood pressure (DPB) (pooled HR 1.056, 95 % CI 1.038-1.074, P < 0.001) were found to be significant predictors for stroke. We did not find a significant association between PP and all-cause mortality (pooled HR 1.022, 95 % CI 0.983-1.063, P = 0.270). We found SBP (pooled HR 1.008, 95 % CI 1.002-1.014, P = 0.012), but not DBP (pooled HR 1.023, 95 % CI 0.964-1.085, P = 0.451) to be significantly associated with all-cause mortality. CONCLUSIONS: Current data confirms that PP is an independent risk factor for stroke but is not a predictor of mortality.

Blood Pressure Reduction in the Acute Phase of an Ischemic Stroke Does Not Improve Short- or Long-Term Dependency or Mortality: A Meta-Analysis of Current Literature.

The purpose of this study was to perform a meta-analysis of current literature to determine whether lowering blood pressure (BP) during the acute phase of an ischemic stroke improves short- and long-term outcomes. PubMed, Cochrane, and Embase were searched until September 5, 2014 using combinations of the search terms: blood pressure reduction, reduced blood pressure, lowering blood pressure, ischemic stroke, acute stroke, and intra-cerebral hemorrhage. Inclusion criteria were randomized controlled trial and patients with acute stroke (ischemic or hemorrhagic) treated with an antihypertensive agent or placebo. Outcome measures were change in systolic and diastolic BP (SBP, DBP) after treatment, and short- and long-term dependency and mortality rates. A total of 459 studies were identified, and ultimately 22 studies were included in the meta-analysis. The total number of participants in the treatment groups was 5672 (range, 6-2308), and in the control groups was 5416 (range, 6-2033). In most studies, more than 50% of the participants were males and the mean age was more than 60 years. The mean follow-up time ranged from 5 days to 12 months. As expected, treatment groups had a greater decrease in BP than control groups, and this effect was seen with different classes of antihypertensive drugs. Short-term and long-term dependency rates were similar between treatment and control groups (short-term dependency: pooled odds ratio [OR] = 1.041, 95% confidence interval [CI]: 0.936-1.159, P = 0.457; long-term dependency: pooled OR = 1.013, 95% CI: 0.915-1.120, P = 0.806). Short-term or long-term mortality was similar between the treatment and control groups (short-term mortality: pooled OR = 1.020, 95% CI: 0.749-1.388, P = .902; long-term mortality: pooled OR = 1.039, 95% CI: 0.883-1.222, P = 0.644). Antihypertensive agents effectively reduce BP during the acute phase of an ischemic stroke, but provide no benefit with respect to short- and long-term dependency and mortality.