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The initial factor in the occurrence, development, and prognosis of cerebral ischemia is vascular dysfunction in the brain, and vascular remodeling of the brain is the key therapeutic target and strategy for ischemic tissue repair. Catalpol is the main active component of the radix of Rehmannia glutinosa Libosch, and it exhibits potential pleiotropic protective effects in many brain-related diseases, including stroke.
The present study was designed to investigate whether catalpol protects vascular structure and promotes angiogenesis in cerebral ischemic rats and to identify its possible mechanisms in vivo and in vitro.
Cerebral ischemic rats and oxygen-glucose deprivation-exposed brain microvascular endothelial cells were used to study the therapeutic potential of catalpol in vivo and in vitro.
First, neurological deficits, histopathological morphology, infarct volume, vascular morphology, vessel density, and angiogenesis in focal cerebral ischemic rats were observed to test the potential treatment efpol protects vascular structure and promotes angiogenesis in focal cerebral ischemic rats and that the mechanism is dependent on HIF-1α/VEGF.
The results of both the in vivo and in vitro studies proved that catalpol protects vascular structure and promotes angiogenesis in focal cerebral ischemic rats and that the mechanism is dependent on HIF-1α/VEGF.
Previously, we have investigated the therapeutic mechanism of Qingzao Jiufei Decoction (QZJFD), a Chinese classic prescription, on acute lung injury (ALI), however, which remained to be further clarified together with the underlying efficacy related compounds for quality markers (Q-markers).
To explore Q-markers of QZJFD on ALI by integrating a stepwise multi-system with 'network pharmacology-metabolomics- pharmacokinetic (PK)/ pharmacodynamic (PD) modeling'.
First, based on in vitro and in vivo component analysis, a network pharmacology strategy was developed to identify active components and potential action mechanism of QZJFD on ALI. Next, studies of poly-pharmacology and non-targeted metabolomics were used to elaborate efficacy and verify network pharmacology results. Then, a comparative PK study on active components in network pharmacology was developed to profile their dynamic laws in vivo under ALI, suggesting Q-marker candidates. Next, quantified analytes with marked PK variations after modeling(methylophiopogonanone A, methylophiopogonanone B), adjuvant (sesamin, ursolic acid, amygdalin), conductant drugs (liquiritin apioside, liquiritigenin and isoliquiritin) in QZJFD, were recognized by substitutability and relevance of plasmatic concentration at various time points.
9 Q-markers for QZJFD on ALI were identified by a stepwise integration strategy, moreover, which was a powerful tool for screening Q-makers involved with the therapeutic action of traditional Chinese medicine (TCM) prescription and promoting the process of TCM modernization and scientification.
9 Q-markers for QZJFD on ALI were identified by a stepwise integration strategy, moreover, which was a powerful tool for screening Q-makers involved with the therapeutic action of traditional Chinese medicine (TCM) prescription and promoting the process of TCM modernization and scientification.
Due to its rarity, few studies have characterized the epidemiology of male breast cancer. GLPG0634 The purpose of this study was to determine survival and risk factors for male breast cancer in a large U.S.
In this study, 19,795 male patients with breast cancer were identified from the National Cancer Database (2004-2014). Patient demographics, tumor characteristics and treatments were analyzed by using descriptive statistics. We used multivariate Cox regression and Kaplan Meier analysis.
Over 10 years, the incidence of male breast cancer increased from 7.2% to 10.3%, while mortality decreased from 11% to 3.8%. Socioeconomic factors predicting mortality included income medium, and high vs low (HR=0.78; 0.68), private vs no insurance (HR=0.73) and the academic research facility vs community cancer center (HR=0.79). Significant predictors of all-cause mortality included age (HR=1.04), tumor size (HR=1.01), hormone receptor expression (HR=0.8) and cancer stage I vs II, III, and IV at the time of diagnosis (HR=1.5, ioeconomic factors, biomarker identification and timely, appropriately chosen treatment are likely to reduce the risk for mortality.
Serous borderline tumors (SBT) are the most common subtype of ovarian borderline tumors with excellent clinical course. However, they can recur or progress to low-grade serous carcinoma (LGSC) in a small proportion of the cases. Beside BRAF and KRAS mutations, copy number alterations (CNA), particularly loss of chromosome 9p21 locus which results in deletion of genes CDKN2A and MTAP, have been suggested to be involved in disease progression. MTAP immunohistochemistry recently has been introduced for mesothelioma as a reliable surrogate marker for the homozygous deletion of chromosome 9p21 locus. Therefore, in the current study, we aimed to evaluate the MTAP loss of expression in serous borderline tumors and low-grade serous carcinomas to identify if it can be used as a marker for prognosis and progression.
Eighty-four total cases of ovarian serous lesions, including 21 cases of serous cystadenomas, 21 cases of serous borderline tumors, 12 cases of low-grade serous carcinomas and 30 cases of high-grade sermors and low-grade serous carcinomas. Our study was limited due to small sample size. However, it showed an association between MTAP loss of expression and adverse clinical behavior in ovarian serous borderline tumors. This supports the role for further investigations in larger series to evaluate the role of MTAP stain as a prognostic marker in these neoplasms.
To our knowledge, this is the first description of MTAP immunohistochemistry in serous borderline tumors and low-grade serous carcinomas. Our study was limited due to small sample size. However, it showed an association between MTAP loss of expression and adverse clinical behavior in ovarian serous borderline tumors. This supports the role for further investigations in larger series to evaluate the role of MTAP stain as a prognostic marker in these neoplasms.The face of a friend indicates safety, the face of a foe can indicate threat. Here, we examine the effects of verbal instructions ('beware of this person') on the perception of unknown persons. Focusing on visual attention, face identity and facial expression information is examined during instructed threat-of-shock or safety. However, shocks never occurred. Participants quickly acquired instructed threat associations, and electrocortical processing differentiated threat- from safe-identities as well as emotional and neutral facial expressions. Importantly, face encoding varied as a joint function of identity and facial expression, as revealed by pronounced N170 amplitudes to smiling threat-identities. Moreover, instructions readily reversed previously learned affective associations leading to attention allocation and memory updating as reflected by N170, EPN and P3 amplitudes toward new threat-identities displaying angry expressions. These findings demonstrate that person perception flexibly re-adjusts according to minimal information. Intriguingly, perceptual biases occur even though the anticipated aversive consequence does not occur, with implications for research on stereotyping and anxious psychopathology.
Anorexia represents a common and debilitating clinical problem in patients with several forms of cancer, in particular lung cancer, but its mechanisms are not completely understood. Recently, the caseinolytic-protease-B (ClpB) homologue protein, produced by common gut bacteria, such as Escherichia coli, was identified as an antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB was previously detected in human plasma and displayed satietogenic properties; however, its possible relevance to cancer anorexia has not yet been investigated.
To address this question, we analyzed plasma ClpB concentrations as well as levels and affinities of anti-ClpB andα-MSH-reactive antibodies in patients with lung cancer with and without anorexia as compared with body mass index-matched healthy controls with normal appetite.
We found that plasma ClpB concentrations were significantly lower in non-anorexic patients with cancer than those of the control group (P=0.028). In contrast, patients with cancer and anorexia had lower levels of anti-ClpB immunoglobulins (Ig)M (P < 0.0001) and of both α-MSH IgM and IgG (P < 0.05) with respect to controls. Moreover, in patients with cancer and anorexia, anti-ClpB IgG showed a trend of lower affinities compared with non-anorexic patients (P=0.05).
Taken together, the results revealed a reduced humoral immune response to ClpB in patients with cancer and anorexia, which may lead to an enhanced satietogenic effect of this enterobacterial protein contributing to the mechanisms of reduced appetite.
Taken together, the results revealed a reduced humoral immune response to ClpB in patients with cancer and anorexia, which may lead to an enhanced satietogenic effect of this enterobacterial protein contributing to the mechanisms of reduced appetite.
Evidence from prospective studies on the association between eating speed and metabolic syndrome is limited. We prospectively investigated the association between eating speed and metabolic syndrome in a Japanese working population.
Participants were 1018 workers (ages 19-68 y) without metabolic syndrome at baseline who completed both baseline and 3-y follow-up surveys. Eating speed was self-reported and categorized as slow, medium, or fast. Metabolic syndrome was defined using criteria recommended in a joint interim statement from several international societies. A multiple logistic regression was used to estimate the odds ratio of metabolic syndrome according to eating speed with adjustment for covariates, including total energy intake.
At the 3-y follow-up, 67 workers (6.6%) were newly identified as having metabolic syndrome. Fast eating speed was significantly associated with increased odds of developing metabolic syndrome, with multivariable-adjusted odds ratios for eating fast of 2.13 (95% confidence intervals, 1.23-3.68) compared with medium eating speed with an adjustment for covariates, including total energy intake. The association remained statistically significant after an additional adjustment for body mass index (BMI) and BMI change between baseline and follow-up surveys (odds ratio 1.95; 95% confidence interval, 1.06-3.56).
Fast eating speed was associated with an increased likelihood of developing metabolic syndrome independently of total energy intake, BMI at baseline, and BMI change during the follow-up period.
Fast eating speed was associated with an increased likelihood of developing metabolic syndrome independently of total energy intake, BMI at baseline, and BMI change during the follow-up period.The COVID-19 pandemic has rapidly spread around the world with significant morbidity and mortality in a subset of patients including the elderly. The poorer outcomes are associated with 'cytokine storm-like' immune responses, otherwise referred to as 'hyperinflammation'. While most of the infected individuals show minimal or no symptoms and recover spontaneously, a small proportion of the patients exhibit severe symptoms characterized by extreme dyspnea and low tissue oxygen levels, with extensive damage to the lungs referred to as acute respiratory distress symptom (ARDS). The consensus is that the hyperinflammatory response of the host is akin to the cytokine storm observed during sepsis and is the major cause of death. Uncertainties remain on the factors that lead to hyperinflammatory response in some but not all individuals. Hyperinflammation is a common feature in different viral infections such as dengue where existing low-titer antibodies to the virus enhances the infection in immune cells through a process called antibody-dependent enhancement or ADE.
Homepage: https://www.selleckchem.com/products/filgotinib.html
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