Objective
To investigate the intranetwork resting state fMRI connectivity within the Salience Network of chronic migraine with and without medication overuse headache.
Methods
We compared 351 pairs ...of intranetwork connectivity in chronic migraine (n = 13) and chronic migraine with medication overuse headache (n = 16) compared to matched controls, and between each chronic migraine subgroup.
Results
Compared to controls, 17 pairs of intranetwork connections in chronic migraine and 27 pairs in chronic migraine with medication overuse headache were decreased. When comparing chronic migraine with medication overuse headache versus chronic migraine, connectivity between bilateral extended amygdala, and between paracingulate to right ventral tegmental area/substantia nigra were decreased in chronic migraine (chronic migraine < chronic migraine with medication overuse headache). Connectivity between left dorsolateral prefrontal cortex to bilateral ventral striatum/pallidum, to bilateral dorsal anterior cingulate cortex; left anterior prefrontal cortex to contralateral orbitofrontal insula; and left ventral striatum/pallidum to ipsilateral supplementary motor area (SMA)/preSMA were decreased in chronic migraine with medication overuse headache (chronic migraine with medication overuse headache < chronic migraine).
Conclusion
Both chronic migraine subgroups had shared intranetwork connectivity abnormality, however, each subgroup had unique pattern of disruption within the salience network. The results suggest that the aberrant assignment of salience to external and internal stimuli plays an important role in chronic migraine and chronic migraine with medication overuse headache interictally, mostly involving mesolimbic pathways (especially bilateral extended amygdala) in chronic migraine, and prefrontal-subcortical limbic pathways in chronic migraine with medication overuse headache.
To evaluate the episodic migraine (EM)-obesity association and the influence of age, race, and sex on this relationship.
We examined the EM-obesity association and the influence of age, race, and sex ...in 3,862 adult participants of both black and white race interviewed in the National Comorbidity Survey Replication. EM diagnostic criteria were based on the International Classification of Headache Disorders. Body mass index was classified as underweight (<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (≥30 kg/m(2)). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for EM were estimated using logistic regression. Models were stratified by age (<50/≥50 years), race (white/black), and sex (male/female).
A total of 188 participants fulfilled criteria for EM. In all participants, the adjusted odds of EM were 81% greater in individuals who were obese compared with those of normal weight (OR 1.81; 95% CI: 1.27-2.57; p = 0.001), with a significant trend of increasing odds of EM with increasing obesity status from normal weight to overweight to obese (p = 0.001). In addition, stratified analyses demonstrated that the odds of EM were greater in obese as compared with normal-weight individuals who were 1) younger than 50 years of age (OR 1.86; 95% CI: 1.20-2.89; p for trend = 0.008), 2) white (OR 2.06; 95% CI: 1.41-3.01; p for trend ≤0.001), or 3) female (OR 1.95; 95% CI: 1.38-2.76; p for trend ≤0.001).
The odds of EM are increased in those with obesity, with the strongest relationships among those younger than 50 years, white individuals, and women.
Genomes of all mammals encode apobec3 genes, which are thought to have a function in intrinsic cellular immunity to several viruses including human immunodeficiency virus type 1 (HIV-1). APOBEC3 (A3) ...proteins are packaged into virions and inhibit retroviral replication in newly infected cells, at least in part by deaminating cytidines on the negative strand DNA intermediates. However, the role of A3 in innate resistance to mouse retroviruses is not understood. Here we show that A3 functions during retroviral infection in vivo and provides partial protection to mice against infection with mouse mammary tumour virus (MMTV). Both mouse A3 and human A3G proteins interacted with the MMTV nucleocapsid in an RNA-dependent fashion and were packaged into virions. In addition, mouse A3-containing and human A3G-containing virions showed a marked decrease in titre. Last, A3-/- mice were more susceptible to MMTV infection, because virus spread was more rapid and extensive than in their wild-type littermates.
Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has ...become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction.
Linked Articles
This article is part of a themed section on Epigenetics and Therapy. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐11
Transcription of HIV provirus is a key step of the viral cycle, and depends on the recruitment of the cellular positive transcription elongation factor b (P-TEFb) to the HIV promoter. The viral ...transactivator Tat can displace P-TEFb from the 7SK small nuclear ribonucleoprotein, where it is bound and inactivated by HEXIM1, and bring it to TAR, which allows the stalled RNA polymerase II to transition to successful transcription elongation. In this study, we designed a chimeric inhibitor of HIV transcription by combining functional domains from HEXIM1 and Tat. The chimera (HT1) potently inhibited gene expression from the HIV promoter, by competing with Tat for TAR and P-TEFb binding, while keeping the latter inactive. HT1 inhibited spreading infection as well as viral reactivation in lymphocyte T cell line models of HIV latency, with little effect on cellular transcription and metabolism. This proof-of-concept study validates an innovative approach to interfering with HIV transcription via peptide mimicry and competition for RNA-protein interactions. HT1 represents a new candidate for HIV therapy, or HIV cure via the proposed block and lock strategy.
Although anti-retroviral therapies have greatly extended the lives of HIV infected individuals, current treatments are unable to completely eliminate virally infected cells. A number of latency ...reversing agents have been proposed for use in a "shock and kill" strategy to reactivate latent HIV, thus making it vulnerable to killing mechanisms. Procyanidin trimer C1 (PC1) is a flavonoid found in multiple plant sources including grape, apple, and cacao, which has antioxidant and anti-inflammatory properties. We determined that PC1 reactivates latent HIV in cell line and primary cell models of HIV, through activation of the MAPK pathway. Notably, PC1 reactivates latent HIV without increasing surface markers of T cell activation. Combining several therapeutics, which activate HIV transcription through different mechanisms, is the most efficient approach to clinically reactivate latent reservoirs. We utilized PC1 (MAPK agonist), kansui (PKC agonist), and JQ1 (BET bromodomain inhibitor) in a triple combination approach to reactivate latent HIV in cell line and primary cell models of HIV latency. When used in combination, low concentrations which fail to reactivate HIV as single treatments, are effective. Thus, several mechanisms, using distinct activation pathways, act together to reactivate latent HIV.
(Headache 2011;51:869‐879)
Migraine and maltreatment are both common conditions that are more prevalent in women. Epidemiological evidence supports an association between childhood abuse and ...headache, as well as pain in general, although some controversy exists based on methodological concerns of studying the influence of remote, traumatic, stigmatizing events in an often depressed population. There is a growing scientific body of knowledge regarding the neurobiological effects of abuse on brain function and structure that suggest a possible role of early life stress in the pathogenesis of migraine, and a differential impact based on sex. Advances in our understanding of the basic mechanisms by which an adverse environment interacts with and changes the genome, may suggest new treatment strategies.
Natural Products and HIV/AIDS Cary, Daniele C; Peterlin, B Matija
AIDS research and human retroviruses,
01/2018, Letnik:
34, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The study of natural products in biomedical research is not a modern concept. Many of the most successful medical therapeutics are derived from natural products, including those studied in the field ...of HIV/AIDS. Biomedical research has a rich history of discovery based on screens of medicinal herbs and traditional medicine practices. Compounds derived from natural products, which repress HIV and those that activate latent HIV, have been reported. It is important to remember the tradition in medical research to derive therapies based on these natural products and to overcome the negative perception of natural products as an "alternative medicine."
To evaluate the intrinsic resting functional connectivity of the default mode network (DMN), salience network (SN), and central executive network (CEN) network in women with chronic migraine (CM), ...and whether clinical features are associated with such abnormalities.
We analyzed resting-state connectivity in 29 women with CM as compared to age- and sex-matched controls. Relationships between clinical characteristics and changes in targeted networks connectivity were evaluated using a multivariate linear regression model.
All 3 major intrinsic brain networks were less coherent in CM (DMN:
= 0.030, SN:
= 0.007, CEN:
= 0.002) as compared to controls. When stratified based on medication overuse headache (MOH) status, CM without MOH (DMN:
= 0.029, SN:
= 0.023, CEN:
= 0.003) and CM with MOH (DMN:
= 0.016, SN:
= 0.016, CEN:
= 0.015) were also less coherent as compared to controls. There was no difference in CM with MOH as compared to CM without MOH (DMN:
= 0.382, SN:
= 0.408, CEN:
= 0.419). The frequency of moderate and severe headache days was associated with decreased connectivity in SN (
= 0.003) and CEN (
= 0.015), while cutaneous allodynia was associated with increased connectivity in SN (
= 0.011).
Our results demonstrated decreased overall resting-state functional connectivity of the 3 major intrinsic brain networks in women with CM, and these patterns were associated with frequency of moderate to severe headache and cutaneous allodynia.
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