Conleywilkinson3184

These results suggest that affective scene representations in the brain are formed temporally in a valence-dependent manner and may be sustained by recurrent neural interactions among distributed brain areas.To estimate microstructure-related parameters from diffusion MRI data, biophysical models make strong, simplifying assumptions about the underlying tissue. The extent to which many of these assumptions are valid remains an open research question. This study was inspired by the disparity between the estimated intra-axonal axial diffusivity from literature and that typically assumed by the Neurite Orientation Dispersion and Density Imaging (NODDI) model (d∥=1.7μm2/ms). We first demonstrate how changing the assumed axial diffusivity results in considerably different NODDI parameter estimates. Second, we illustrate the ability to estimate axial diffusivity as a free parameter of the model using high b-value data and an adapted NODDI framework. Using both simulated and in vivo data we investigate the impact of fitting to either real-valued or magnitude data, with Gaussian and Rician noise characteristics respectively, and what happens if we get the noise assumptions wrong in this high b-value and thus low SNR regime. Our results from real-valued human data estimate intra-axonal axial diffusivities of ∼2-2.5μm2/ms, in line with current literature. Crucially, our results demonstrate the importance of accounting for both a rectified noise floor and/or a signal offset to avoid biased parameter estimates when dealing with low SNR data.

Decoction is the most common form of administering traditional Chinese medicine (TCM). During the preparation of decoction, the high temperature and complex chemical environment result in the formation of complex and multiple phases. The differences in drug components in different phases induce gastrointestinal absorption and physiological response. Nux vomica (Strychnos nux-vomica L) is a typical toxic TCM used in China, with remarkable pharmacological activity. In order to reduce its toxicity, nux vomica (NV) is often decocted with Glycyrrhiza glabra (GG) in clinic, and the detoxification mechanism has always been the focus of research interest. Most studies investigated the compatibility of NV-GG, but the in vivo behavior of individual constituents based on phase state has yet to be elucidated.

To investigate the pharmacokinetic behavior of typical toxic components in different phase states of "NV-GG decoction" in rat plasma.

The sediment, suspension, colloid and true solution of "NV-GG decoction" walized to study the pharmacokinetics of different phase states of "NV-GG decoction". Among the four phases, the deposition phase contributed to a large proportion of the in vivo kinetic behavior similar to that of sustained-release preparations, with slow absorption of toxic components and prolonged peak time. The pharmacokinetic parameters and plasma concentration-time curves of each phase can be used to study toxicity reduction of NV-GG and increase its biocompatibility.

In the long history of traditional Chinese medicine, Panax notoginseng has been used as a key herb for the treatment of blood diseases. Brain microvessels support adequate blood circulation to maintain normal physiological function, therefore, brain microcirculation disorder is an important therapeutic target for various brain diseases. However, the role of Xueshuantong (XST) injection composed of saponins from P. Notoginseng (PNS) in the amelioration of cerebral microcirculation disorder is unclear.

Cerebral microcirculation disorder and inflammation play a vital role in stroke. Capillary endothelial cells and adjacent tight junctions are fundamental to the structure and function of cerebrovascule. XST injection has been used clinically in the treatment of stroke, but no studies have reported its indication in cerebral microcirculation disorder. This study is to explore the action and mechanism of XST injection in the alleviation of cerebral microcirculation disorder in middle cerebral artery occlusion/rAT3 and NF-κB signaling pathways. The novel findings may provide theoretical basis for the clinical application in the treatment of cerebral microcirculation disorder.

XST injection improved cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. The novel findings may provide theoretical basis for the clinical application in the treatment of cerebral microcirculation disorder.

Xiang-lian pill, consisting of Coptis chinensis Franch. coprocessed with Tetradium ruticarpum (A.Juss.) T.G.Hartley (Yu-huang-lian) and Aucklandia lappa DC. (Mu-xiang), is traditionally used to relieve fever, abdominal pain, and gastrointestinal inflammatory symptoms observed in patients with malignancies of the gastrointestinal tract. Each of the three herbs contained in Xiang-lian pill has been indicated to have anticancer effects on a variety of cancers, but its effects on pancreatic cancer remain unexplored. The main extracts of these herbs have anti-pancreatic cancer effects, but the comprehensive mechanism of this compound prescription of Xiang-lian pill in pancreatic cancer remains to be revealed.

To explore the main active ingredients, potential anti-pancreatic cancer targets, and related mechanisms of the Xiang-lian pill and to determine its therapeutic value in vivo.

Network pharmacology and bioinformatics analysis were applied to screen the potential effective ingredients and key targets. Liqrapeutic mechanism of Xiang-lian pill.

Back pain is one of the leading causes of disability and decreased quality of life. In this study, we examined the association between back pain and major depressive disorder (MDD) in six low- and middle-income countries. We also examined the association of back pain duration and severity with MDD among middle-aged and older adults in these countries.

Nationally representative data from the World Health Organization's Study on global AGEing and adult health (WHO-SAGE) consisting of 33,878 middle-aged and older adults aged 50years or above were analysed. The linkages of back pain, pain duration and severity with MDD were examined using multivariable logistic regression analyses.

Across six countries, the prevalence of MDD was higher among middle-aged and older adults who reported back pain than those who did not report back pain (14.5% vs 4.5%). In the pooled data, middle-aged and older adults who suffered from back pain had higher odds of depression [adjusted odds ratio (aOR) 2.41, confidence interval (CI) 2.19-2.64] compared to those with no back pain. Particularly, the association was stronger in Ghana [aOR 4.78] and South Africa [aOR 2.42]. Further, the association was stronger for those who experienced back pain for >2weeks as well as those who reported severe and extreme back pain than those with no back pain across all the countries.

In this study, the association of back pain and its duration and severity with MDD is consistent and significant among middle-aged and older adults in six countries. Government policies should consider the role of back pain in improving the mental health of middle-aged and older adults.

In this study, the association of back pain and its duration and severity with MDD is consistent and significant among middle-aged and older adults in six countries. Government policies should consider the role of back pain in improving the mental health of middle-aged and older adults.Since the introduction of the cancer stem cell (CSC) paradigm, significant advances have been made in understanding the functional and biological plasticity of these elusive components in malignancies. Endowed with self-renewing abilities and multilineage differentiation potential, CSCs have emerged as cellular drivers of virtually all facets of tumor biology, including metastasis, tumor recurrence/relapse, and drug resistance. The functional and biological characteristics of CSCs, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation are regulated by an array of extracellular factors, signaling pathways, and pluripotent transcriptional factors. Besides the well-characterized regulatory role of transcription factors OCT4, SOX2, NANOG, KLF4, and MYC in CSCs, evidence for the central role of Forkhead box transcription factor FOXM1 in the establishment, maintenance, and functions of CSCs is accumulating. Conventionally identified as a master regulator of the cell cycle, a comprehensive understanding of this molecule has revealed its multifarious oncogenic potential and uncovered its role in angiogenesis, invasion, migration, self-renewal, and drug resistance. This review compiles the large body of literature that has accumulated in recent years that provides evidence for the mechanisms by which FOXM1 expression promotes stemness in glioblastoma, breast, colon, ovarian, lung, hepatic, and pancreatic carcinomas. We have also compiled the data showing the association of stem cell mediators with FOXM1 using TCGA mRNA expression data. Further, the prognostic importance of FOXM1 and other stem cell markers is presented. The delineation of FOXM1-mediated regulation of CSCs can aid in the development of molecularly targeted pharmacological approaches directed at the selective eradication of CSCs in several human malignancies.Defective DNA repair pathways contribute to the development of chronic kidney disease (CKD) in humans. However, the molecular mechanisms underlying DNA damage-induced CKD pathogenesis are not well understood. selleck chemicals Here, we investigated the role of tubular cell DNA damage in the pathogenesis of CKD using mice in which the DNA repair protein Fan1 was knocked out. The phenotype of these mice is orthologous to the human DNA damage syndrome, karyomegalic interstitial nephritis (KIN). Inactivation of Fan1 in kidney proximal tubule cells sensitized the kidneys to genotoxic and obstructive injury characterized by replication stress and persistent DNA damage response activity. Accumulation of DNA damage in Fan1 tubular cells induced epithelial dedifferentiation and tubular injury. Characteristic to KIN, cells with chronic DNA damage failed to complete mitosis and underwent polyploidization. In vitro and in vivo studies showed that polyploidization was caused by the overexpression of DNA replication factors CDT1 and CDC6 in FAN1 deficient cells. Mechanistically, inhibiting DNA replication with Roscovitine reduced tubular injury, blocked the development of KIN and mitigated kidney function in these Fan1 knockout mice. Thus, our data delineate a mechanistic pathway by which persistent DNA damage in the kidney tubular cells leads to kidney injury and development of CKD. Furthermore, therapeutic modulation of cell cycle activity may provide an opportunity to mitigate the DNA damage response induced CKD progression.Anthropogenic activity has created unique environmental drivers, which may interact to produce unexpected effects. My aim was to conduct a systematic review of the interactive effects of anthropogenic drivers on endocrine responses in non-human animals. The interaction between temperature and light can disrupt reproduction and growth by impacting gonadotropins, thyroid hormones, melatonin, and growth hormone. Temperature and endocrine disrupting compounds (EDCs) interact to modify reproduction with differential effects across generations. The combined effects of light and EDCs can be anxiogenic, so that light-at-night could increase anxiety in wildlife. Light and noise increase glucocorticoid release by themselves, and together can modify interactions between individuals and their environment. The literature detailing interactions between drivers is relatively sparse and there is a need to extend research to a broader range of taxa and interactions. I suggest that incorporating endocrine responses into Adverse Outcome Pathways would be beneficial to improve predictions of environmental effects.