Evaluation of the antioxidant, anti-inflammatory and hepatoprotective properties of vanillin in carbon tetrachloride-treated rats

The antioxidant and anti-inflammatory effects of vanillin are considered as important forces in the protection against liver injury and fibrosis. This study investigated the protective effects of vanillin against carbon tetrachoride (CCl(4))-induced hepatotoxicity in rat. Pretreatment with vanillin prior the administration of CCl(4) significantly prevented the decrease of protein synthesis and the increase in plasma alanine (ALT) and aspartate (AST) aminotransferases. Furthermore, it inhibited hepatic lipid peroxidation (MDA) and protein carbonyl (PCO) formation and attenuated the (CCl(4))-mediated depletion of antioxidant enzyme catalase and superoxide dismutase (SOD) activities and glutathione level (GSH) in the liver. In addition, vanillin markedly attenuated the expression levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and prevented CCl(4)-induced hepatic cell alteration and necrosis, as indicated by liver histopathology. These findings suggest that the antioxidant and anti-inflammatory effects of vanillin against CCl(4)-induced acute liver injury may involve its ability to block CCl(4)-generated free radicals.     

Tonic and phasic descending dopaminergic controls of nociceptive transmission in the medullary dorsal horn

The transfer of nociceptive information at the level of dorsal horn is subject to extensive processing by both local segmental and supraspinal mechanisms, including descending dopaminergic controls, originating from the hypothalamic A11 nucleus. The inhibitory role of dopamine on evoked pain via activation of D2-like receptors at the level of the dorsal horn is well established. Here, by use of behavioral, electrophysiological, and anatomical techniques, we examined within the trigeminal sensory complex, first, whether descending dopaminergic controls also modulate pain behavior after an inflammatory insult, and second, under which physiological conditions these descending dopaminergic controls are actually recruited. We show that D2 receptors are mostly located within superficial medullary dorsal horn where trigeminal nociceptive fibers abut. Activating these D2-like receptors inhibits, whereas blocking them enhances, both formalin- and capsaicin-evoked pain behavior and C-fiber-evoked action potential firing of trigeminal wide dynamic range (WDR) neurons. Moreover, windup and diffuse noxious inhibitory controls (DNIC), 2 dynamic properties of C-fiber-evoked firing of WDR neurons, are inhibited by activating and blocking, respectively, these D2-like receptors. Altogether, our results are consistent with a tonic inhibition of the trigeminal nociceptive input by descending dopaminergic controls via activation of D2-like receptors at the level of superficial medullary dorsal horn. Such dopamine-dependent tonic inhibition of nociceptive information can be dynamically modulated by pain. This suggests that dysregulation of descending dopaminergic controls should translate in patients into diffuse, cephalic, and extracephalic pain symptoms—spontaneous pain, decreased pain thresholds, deficient DNIC, or some combination of these.     

Clinical Profile, Quality of Care, and Recurrence in Arab-American and Caucasians Prostate Cancer Patients in Michigan

Prostate cancer is the most common cancer among men in the United States with striking differences in incidence and mortality among ethnic groups. Michigan has one of the largest concentrations of Arab Americans (AAs) in the U.S. and little is known about this ethnic minority with respect to prostate cancer. This study investigated differences in clinical profile, quality of care, and recurrence among prostate cancer survivors comparing AAs and Caucasian Americans (CAs). Participants in this study included 2499 prostate cancer survivors from the Michigan Cancer Registry from 1985 to 2004. Participants completed surveys regarding health-seeking behavior, post-treatment symptoms, quality of care and recurrence. Ethnicity was self-reported and AAs and CAs were compared with respect to clinical profile, quality of care, and recurrence. There were 52 AAs and 1886 CAs patients with AAs being younger ( $ \bar{x} $ age 68.3 ± SD 21.4 years, $ \bar{x} $ age 72.3 ± SD 14.1 years, for AAs and CAs, respectively) (P = 0.05). AAs had lower socioeconomic standard than CAs (34 vs. 10.6 %, <$20,000 yearly income/year; for AAs vs. CAs, respectively) (P < 0.0001). AAs reported poorer health than AAs (7.7 vs. 3.0 % for AAs vs. CAs, respectively) (P < 0.0001). AAs were more likely to visit specialists for prostate follow-up (44.5 vs. 19.7 % visited a specialist, for AAs vs. CAs respectively) (P < 0.0001) and received supplementary healthcare workers (13 % of AAs vs. 3.1 % CAs) (P = 0.032). In addition, AAs reported higher occurrence of urinary incontinence compared to CAs (67.4 vs. 60.4 %, for AAs vs. CAs, respectively) (P = 0.001). Ethnic background was not a predictor of recurrence [(Odds ratio (OR) = 1.1 (95 % confidence intervals CI = 0.40, 2.9)] (P = 0.873) even after adjusting for age, PSA levels within the last 2 years, metastasis and hormonal therapy. While AAs prostate cancer patients were different from CAs in age, income, seeking medical care, and health reporting, ethnic background was not a predictor of recurrence. Future studies of the impact of socioeconomic, demographic and cultural factors, and health care seeking behavior on long-term survival of prostate cancer in AAs and other ethnic minorities are warranted.     

Effects of methanol extracts from roots,leaves, and fruits of the Lebanese strawberry tree (Arbutus andrachne) on cardiac function together with their antioxidant activity

Context: Several plant-derived natural products have been used in clinical phase for applications in neurological, cardiovascular, and inflammatory diseases. Arbutus andrachne L. (Ericacea) is an evergreen shrub native to the Mediterranean region. Traditionally, the fruits and leaves of Arbutus tree are well known and used as antiseptics, diuretics, blood tonic, and laxatives.

Objective: Data regarding the biological effects of compounds derived from the Lebanese Arbutus andrachne are not available. In the present work, we studied the antioxidant activity of methanol extracts of leaves, fruits, and roots of the plant against electrolysis; together with their effects on the cardiodynamics of isolated perfused rabbit hearts.

Materials and methods: In vitro electrolysis of the different root, leaves, and fruits methanol extracts was evaluated by the amount of free radicals that has been reduced by increasing the concentration of root extracts ranging from 0.5 to 2?mg after 1, 2, 3, and 4?min. Left ventricular pressure (LVP), heart rate (HR), and coronary flow (CR) were investigated in isolated rabbit heart after administration of 0.5, 1, 2, and 2?mg of each methanol extracts plotted against time (0, 0.5, 1.5, 5, and 10?min), according to the Langendorff method. Lipid peroxidation study was performed by the colorimetric method on myocard tissue after incubation with 500?μl of the different methanol extracts. The amount of MDA was determined at 500?nm absorbance after 5?min incubation.

Results: Among the different methanol extracts, the roots showed the highest in vitro antioxidant activity, particularly observed at concentration of 2?mg which completely inhibits free radical generation after 4?min. LVP decreases by 32% at the dose of 2?mg of root extracts after 5?min. No significant effect was observed by the three tested extracts on the heart rate. The three methanol extracts did not show any significant effect on the coronary flow. Moreover, the roots show an increase in the coronary flow at a concentration of 1 and 2?mg/ml during 1?min. Electrolysis on heart tissue treated with the roots extracts shows a decrease in the MDA level from 70.51?±?6.71 to 48.58?±?4.15 nmole/g of tissue.

Discussion and conclusion: Methanol extracts of the roots possess antihypertensive effect that may result from its ability to decrease the LVP together with its protective role by inhibiting free radical generation and significantly decreasing the MDA level of heart tissue.     

Identification of Parkinson's Disease Subtypes from Resting-State Electroencephalography

Background

Parkinson's disease (PD) patients present with a heterogeneous clinical phenotype, including motor, cognitive, sleep, and affective disruptions. However, this heterogeneity is often either ignored or assessed using only clinical assessments.

Objectives

We aimed to identify different PD sub-phenotypes in a longitudinal follow-up analysis and their electrophysiological profile based on resting-state electroencephalography (RS-EEG) and to assess their clinical significance over the course of the disease.

Methods

Using electrophysiological features obtained from RS-EEG recordings and data-driven methods (similarity network fusion and source-space spectral analysis), we have performed a clustering analysis to identify disease sub-phenotypes and we examined whether their different patterns of disruption are predictive of disease outcome.

Results

We showed that PD patients (n = 44) can be sub-grouped into three phenotypes with distinct electrophysiological profiles. These clusters are characterized by different levels of disruptions in the somatomotor network (Δ and β band), the frontotemporal network (α2 band) and the default mode network (α1 band), which consistently correlate with clinical profiles and disease courses. These clusters are classified into either moderate (only-motor) or mild-to-severe (diffuse) disease. We showed that EEG features can predict cognitive evolution of PD patients from baseline, when the cognitive clinical scores were overlapped.

Conclusions

The identification of novel PD subtypes based on electrical brain activity signatures may provide a more accurate prognosis in individual patients in clinical practice and help to stratify subgroups in clinical trials. Innovative profiling in PD can also support new therapeutic strategies that are brain-based and designed to modulate brain activity disruption. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Histidine kinases and histidine phosphorylated proteins in mammalian cell biology,signal transduction and cancer

Intensive investigation of protein tyrosine, serine and threonine phosphorylation has lead to advances in signal transduction research and cancer treatment. This feature summarizes research on mammalian proteins exhibiting histidine phosphorylation. Histidine kinases are well known in prokaryotic and lower eukaryotic systems where they form the 'two-component' signal transduction system. The relative invisibility of histidine phosphorylation in mammalian cells may result from technical obstacles such as its acid lability, which precludes detection in electrophoretic systems, amino acid sequencing, etc. Emerging data have identified mammalian histidine kinases for the kinase suppressor of ras, a scaffold molecule for the Map kinase pathway, as well as histone H4, aldolase C and the beta-subunit of heterotrimeric G proteins. Additional mammalian proteins of interest to signal transduction and cancer research exhibit histidine phosphorylation, including P-selectin, annexin I and the 20S proteasome. Other candidate histidine phosphorylated proteins are identified. These data suggest the existence of another series of phosphorylation patterns in signal transduction.