Urinary Proteomics Reveals Promising Biomarkers in Menstrually Related and Post-Menopause Migraine.
Ontology highlight
ABSTRACT:
SUBMITTER: Bellei E
PROVIDER: S-EPMC8123166 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundCyclic hormonal fluctuations influence migraine incidence and severity. Previously, we described reduced menstrual cyclicity in estradiol levels and dermal blood flow reaction to capsaicin in female migraineurs. It is unclear whether pain perception in women with migraine is influenced by the menstrual cycle.MethodsWomen with menstrually-related migraine (n = 14), healthy age-matched controls (n = 10) and postmenopausal women (n = 15) were asked to grade trigeminal and non-trigeminal painful stimuli on a numeric pain rating scale on menstrual cycle day 19-21 (mid-luteal) and day 1-2 (early follicular).ResultsIn women with menstrually-related migraine, trigeminal pain remained low throughout the cycle. Controls showed increased trigeminal pain during the mid-luteal phase compared to the early follicular phase. Changes throughout the cycle were significantly different between women with MRM and controls.ConclusionThe compromised menstrual cyclicity of pain perception in women with menstrually-related migraine parallels our earlier findings on estradiol levels and dermal blood flow.
| S-EPMC7961656 | biostudies-literature
Project description:BACKGROUND: Menstrually related migraine (MRM) affects more than half of female migraineurs. Because such migraines are often predictable, they provide a suitable target for treatment in the mild pain phase. The present study was designed to provide prospective data on the efficacy of almotriptan for treatment of MRM. METHODS: Premenopausal women with MRM were randomized to almotriptan (N = 74) or placebo (N = 73), taken at onset of the first perimenstrual migraine. Patients crossed over to the other treatment for the first perimenstrual migraine of their second cycle, followed by a two-month open-label almotriptan treatment period. RESULTS: Significantly more patients were pain-free at two hours (risk ratio [RR] = 1.81; p = .0008), pain-free from 2-24 hours with no rescue medication (RR = 1.99; p = .0022), and pain-free from 2-24 hours with no rescue medication or adverse events (RR = 1.94; p = .0061) with almotriptan versus placebo. Nausea (p = .0007) and photophobia (p = .0083) at two hours were significantly less frequent with almotriptan. Almotriptan efficacy was consistent between three attacks, with 56.2% of patients pain-free at two hours at least twice. Adverse events were similar with almotriptan and placebo. CONCLUSION: Almotriptan was significantly more effective than placebo in women with MRM attacks, with consistent efficacy in longer-term follow-up.
| S-EPMC3057443 | biostudies-literature
Project description:BackgroundReduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30).MethodsParticipants were women with migraine afferent to a headache centre; controls were female patients' acquaintances. Serum samples obtained were analyzed by HPLC-ESI-MS/MS.ResultsIn menstrually-related migraine and postmenopausal migraine groups, allopregnanolone levels were lower than in the respective control groups (fertile age and post-menopause) (p < 0.001, one-way analysis of variance followed by Tukey-Kramer post-hoc comparison test) while progesterone and testosterone levels were similar. By grouping together patients with migraine, allopregnanolone levels were inversely correlated with the number of years and days of migraine/3 months (p ≤ 0.005, linear regression analysis).ConclusionDecreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.
| S-EPMC7575305 | biostudies-literature
Project description:BackgroundTargeted proteomics, which involves quantitative analysis of targeted proteins using selected reaction monitoring (SRM) mass spectrometry, has emerged as a new methodology for discovery of clinical biomarkers. In this study, we used targeted serum proteomics to identify circulating biomarkers for prediction of disease activity and organ involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsA large-scale SRM assay targeting 135 biomarker candidates was established using a triple-quadrupole mass spectrometer coupled with nanoflow liquid chromatography. Target proteins in serum samples from patients in the active and remission (6 months after treatment) stages were quantified using the established assays. Identified marker candidates were further validated by enzyme-linked immunosorbent assay using serum samples (n?=?169) collected in a large-cohort Japanese study (the RemIT-JAV-RPGN study).ResultsOur proteomic analysis identified the following proteins as biomarkers for discriminating patients with highly active AAV from those in remission or healthy control subjects: tenascin C (TNC), C-reactive protein (CRP), tissue inhibitor of metalloproteinase 1 (TIMP1), leucine-rich alpha-2-glycoprotein 1, S100A8/A9, CD93, matrix metalloproteinase 9, and transketolase (TKT). Of these, TIMP1 was the best-performing marker of disease activity, allowing distinction between mildly active AAV and remission. Moreover, in contrast to CRP, serum levels of TIMP1 in patients with active AAV were significantly higher than those in patients with infectious diseases. The serum levels of TKT and CD93 were higher in patients with renal involvement than in those without, and they predicted kidney outcome. The level of circulating TNC was elevated significantly in patients with lung infiltration. AAV severity was associated with markers reflecting organ involvement (TKT, CD93, and TNC) rather than inflammation. The eight markers and myeloperoxidase (MPO)-ANCA were clustered into three groups: MPO-ANCA, renal involvement (TKT and CD93), and inflammation (the other six markers).ConclusionsWe have identified promising biomarkers of disease activity, disease severity, and organ involvement in AAV with a targeted proteomics approach using serum samples obtained from a large-cohort Japanese study. Especially, our analysis demonstrated the effectiveness of TIMP1 as a marker of AAV activity. In addition, we identified TKT and CD93 as novel markers for evaluation of renal involvement and kidney outcome in AAV.
| S-EPMC5622475 | biostudies-literature
Project description:About 10% of Japanese female athletes are afflicted by menstrually-related edema, mainly in the lower limbs, and, with few studies on this problem, the effect on performance remains unclear.To quantitatively evaluate fluid retention in the calf in female students over their menstrual cycle using magnetic resonance imaging (MRI) and to determine the relationship of MRI changes and athletic performance.The menstrual cycle was divided into 5 phases: menstrual, follicular, ovulatory, early luteal, and late luteal with sampling done in either morning (AM) or afternoon (PM) sessions. At each phase, MRI of the calf (7:00-8:00, 14:00-16:00), body composition and hormones (7:00-8:00), and athletic performance (14:00-16:00) were evaluated.13 adult healthy Japanese female students with eumenorrhea.Estradiol levels decreased significantly in the menstrual phase and the follicular phase compared to the early luteal phase (P = 0.001, P = 0.024 respectively). Menstrual phase estradiol levels were significantly lower compared to the ovulatory phase (P = 0.015), and the late luteal phase (P = 0.003). Progesterone levels decreased significantly in the menstrual phase and the follicular phase compared to the ovulatory phase (P = 0.012, P = 0.009 respectively), the early luteal phase (both P = 0.007), and the late luteal phase (P = 0.028, P = 0.029 respectively), and it along with a significant decrease in the ovulatory phase compared to the early luteal phase (P = 0.010). AM T2 signals were significantly lower in the menstrual phase compared to the ovulatory phase (P = 0.043) but not other phases. PM T2 signals increased significantly in the menstrual phase compared to the follicular phase (P = 0.003), ovulatory phase (P = 0.009), and the late luteal phase (P = 0.032), and the difference between the AM and PM values increased significantly in the menstrual phase compared to the other 4 phases (P<0.01). A negative correlation between fluid retention and agility was observed.In female students fluid retention during the menstrual phase could be a factor that influences athletic agility.
| S-EPMC5783373 | biostudies-literature
Project description:BackgroundOral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need.Methodology/principal findingsTo discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells.Conclusions/significanceSalivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early.
| S-EPMC2887353 | biostudies-literature
Project description:Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development.
| S-EPMC10651172 | biostudies-literature
Project description:PurposeTo identify noninvasive immune biomarkers of exercise-induced immunosuppression using the iTRAQ proteomics technique.MethodsFifteen healthy males were recruited and subjected to a four-week incremental treadmill running training program. After each week of training, WBC counts and CD4+ and CD8+ lymphocytes were measured to monitor the immune function status. iTRAQ proteomics technology was used to identify differential proteins and their characteristics in urine.ResultsOur data showed that the WBC counts, CD4+ lymphocytes, and CD4+/CD8+ ratio decreased by more than 10% after four weeks of training, suggesting exercise-induced immunosuppression. A total of 1854 proteins were identified in urine during the incremental running using the iTRAQ technology. Compared with the urine before training, there were 89, 52, 77, and 148 proteins significantly upregulated and 66, 27, 68, and 114 proteins significantly downregulated after each week, respectively. Among them, four upregulated proteins, SEMG-1, PIP, PDGFRL, and NDPK, increased their abundance with the increased exercise intensity. Bioinformatics analysis indicates that these proteins are involved in stress response and immune function.ConclusionFour weeks of incremental treadmill running induced immunosuppression in healthy males. By using iTRAQ proteomics, four proteins in the urine, SEMG-1, PIP, PDGFRL, and NDPK, were found to increase incrementally with the increased exercise intensity, which have the potential to be used as noninvasive immune biomarkers of exercise-induced immunosuppression.
| S-EPMC7003279 | biostudies-literature
Project description:Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (? 6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.
| S-EPMC3102389 | biostudies-other
Project description:Clinical data have been equivocal and controversial as to the benefits to the brain and cognition of hormone therapy (HT) in postmenopausal women. Recent reevaluation of the role of estrogens proposed that HT may effectively prevent the deleterious effects of aging on cognition, and reduces the risks of dementia, including Alzheimer's disease, if initiated early at the beginning of menopause. Yet, little is known about the effects of HT on brain activation related to cognitive control, the ability to make flexible decisions in relation to internal goals. Here, we used fMRI to directly test for a modulation of sequential 17β estradiol (2 mg/day) plus oral progesterone (100 mg/day) on task switching-related brain activity in women at early postmenopause. The results showed that HT enhanced dorsolateral prefrontal cortex recruitment during task switching. Between-subjects correlation analyses revealed that women who engaged more the dorsolateral prefrontal cortex showed higher task switching performance after HT administration. These results suggest that HT, when taken early at the beginning of postmenopause, may have beneficial effect on cognitive control prefrontal mechanisms. Together, these findings demonstrate that HT can prevent the appearance of reduced prefrontal cortex activity, a neurophysiological measure observed both in healthy aging and early dementia.
| S-EPMC5359606 | biostudies-literature