Inflammation plays a crucial role in the pathogenesis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Our study aimed to analyse previous inconsistent results of inflammatory markers ...in AD and MCI quantitatively.
Studies reporting concentrations of peripheral or cerebrospinal fluid (CSF) markers were included, and eligible data on AD, MCI and control were extracted. Pooled Hedges's g was adopted to illustrate comparisons, and various confounding factors were used to explore sources of heterogeneity.
A total of 170 studies were included in the meta-analysis and systematic review, which demonstrated increased peripheral levels of high-sensitivity C reactive protein (Hedges's g 0.281, p<0.05), interleukin-6 (IL-6) (0.429, p<0.005), soluble tumour necrosis factor receptor 1 (sTNFR1) (0.763, p<0.05), soluble tumour necrosis factor receptor 2 (sTNFR2) (0.354, p<0.005), alpha1-antichymotrypsin (α1-ACT) (1.217, p<0.005), IL-1β (0.615, p<0.05) and soluble CD40 ligand (0.868, p<0.005), and CSF levels of IL-10 (0.434, p<0.05), monocyte chemoattractant protein-1 (MCP-1) (0.798, p<0.005), transforming growth factor-beta 1 (1.009, p<0.05), soluble triggering receptor expressed on myeloid cells2 (sTREM2) (0.587, p<0.001), YKL-40 (0.849, p<0.001), α1-ACT (0.638, p<0.001), nerve growth factor (5.475, p<0.005) and visinin-like protein-1 (VILIP-1) (0.677, p<0.005), in AD compared with the control. Higher levels of sTNFR2 (0.265, p<0.05), IL-6 (0.129, p<0.05) and MCP-1 (0.779, p<0.05) and lower levels of IL-8 (-1.293, p<0.05) in the periphery, as well as elevated concentrations of YKL-40 (0.373, p<0.05), VILIP-1 (0.534, p<0.005) and sTREM2 (0.695, p<0.05) in CSF, were shown in MCI compared with the control. Additionally, increased peripheral sTNFR1 (0.582, p<0.05) and sTNFR2 (0.254, p<0.05) levels were observed in AD compared with MCI.
Significantly altered levels of inflammatory markers were verified in comparison between AD, MCI and control, supporting the notion that AD and MCI are accompanied by inflammatory responses in both the periphery and CSF.
Controversies persist regarding the association between blood pressure (BP) and the risks of cognitive impairment and dementia due to inconsistent definitions of BP exposure and varying population ...characteristics. Here, we searched PubMed and performed a meta-analysis of the influence of BP exposure on the risks of cognitive disorders in prospective studies. Dose-response analyses were performed to illustrate the existence of linear/nonlinear relationships. The credibility of each meta-analysis was evaluated according to the risk of bias, inconsistency, and imprecision. Of the 31 628 citations, 209 were included in our systematic review, among which 136 were eligible for the meta-analysis. Overall, stronger associations were found in midlife than late-life. Moderate-quality evidence indicated that midlife hypertension was related to a 1.19- to 1.55-fold excess risk of cognitive disorders. Dose-response analyses of 5 studies indicated that midlife systolic BP >130 mm Hg was associated with an increased risk of cognitive disorders. With regard to BP exposure in late-life, high systolic BP, low diastolic BP, excessive BP variability, and orthostatic hypotension were all associated with an increased dementia risk. Encouragingly, the use of antihypertensive medications exhibited a 21% reduction in dementia risk. The U-shaped dose-response curve indicated that the protective window of diastolic BP level was between 90 and 100 mm Hg for low risk of Alzheimer disease. The relationships between BP variables and cognitive disorders are age- and BP type-dependent. Antihypertensive medications were associated with a reduced risk of dementia. However, the optimal dose, duration, and type for preventing cognitive disorders warrant further investigation.
•Pre-heated WPI was treated by high intensity ultrasound (HUS∼107Wcm−2).•The treated WPI solution was used to form GDL-induced gels (GIWG).•Particle size and free sulfhydryl (-SH) content of ...pre-heated WPI were changed.•Water holding capacity, gel strength and gel firmness of GIWG increased after HUS treatment.•Rheological properties, free -SH content and chemical interactions were affected.
Pre-heated whey protein isolate (WPI) solution (10% w/v, 85°C for 30min) was prepared and subjected to high-intensity ultrasound (HUS, 20kHz) at different durations (5–40min) before acidification to determine the effects of HUS on glucono-δ-lactone (GDL)-induced gelation properties of whey protein gel. Results showed that HUS reduced the particle size and increased surface free sulfhydryl groups of pre-heated whey protein solution. Free sulfhydryl (-SH) content of the acid-induced WPI gels (GIWG) and protein solubility in presence of 8M urea were significantly reduced (P<0.05) by HUS (20 or 40min), indicating that HUS facilitated formation of more disulfide bonds during/after the gelation process. HUS significantly increased (P<0.05) the water holding capacity (WHC), gel strength, gel firmness (G′) as well as the frequency dependence of GIWG. The WHC, gel strength and gel firmness were positively correlated with surface free -SH content of pre-heated WPI and negatively correlated with particle size of pre-heated WPI and free -SH content of GIWG. The results indicated that high intensity ultrasound could be used for modifying whey protein to improve its gelling properties.
This paper investigates the effects of freeze‐thaw (FT) fatigue damage on the cracking behaviors of sandstone specimens containing two unparallel fissures under uniaxial compression. First, the ...effects of FT fatigue damage and fissure angle on the mechanical properties of sandstone specimens are analyzed. Second, the real‐time cracking process of sandstone specimens is captured by a high‐speed digital video camera system. Seven crack coalescence patterns are observed in this experiment. Local strong fatigue‐damaged zones, which are visualized as white zones, are observed in the specimens subjected to FT cycles during loading. Finally, scanning electron microscopy (SEM) observations show that the local strong fatigue‐damaged zones mainly consisted of microcracks and micropores induced by the FT fatigue damage. These experimental results are helpful for improving the understanding of the cracking process in cold‐region engineering.
Lutein is a hydrophobic carotenoid that has multiple health functions. However, the application of lutein is limited due to its poor solubility in water and instability under certain conditions ...during storage. Hereby we generated lutein loaded nano-emulsions using whey protein isolate (WPI) or polymerized whey protein isolate (PWP) with assistance of high intensity ultrasound and evaluate their stability during storage at different conditions. We measured the particle size, zeta-potential, physical stability and lutein content change. Results showed that the PWP based nano-emulsion system was not stable in the tested Oil/Water/Ethanol system indicated by the appearance of stratification within only one week. The WPI based nano-emulsion system showed stable physiochemical stability during the storage at 4°C. The lutein content of the system was reduced by only 4% after four weeks storage at 4°C. In conclusion, our whey protein based nano-emulsion system provides a promising strategy for encapsulation of lutein or other hydrophobic bioactive molecules to expand their applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Midlife underweight, midlife obesity and late-life underweight increase dementia risk.•Late-life overweight and obesity conferred 21% and 25% reduced dementia risk.•ACD risk in midlife was ...significantly elevated when BMI surpassed 29 kg/m2.•AD risk in midlife was significantly elevated when BMI surpassed 30 kg/m2.•VaD risk in midlife was significantly elevated when BMI surpassed 32 kg/m2.•AD risk in late-life was decreased in the case of BMI cutoff under 27 kg/m2.
Controversies persist about the associations of body mass index (BMI) with risk of cognitive impairment and dementia. This study aimed to evaluate these associations from various aspects, in which Embase, PubMed and Cochrane databases were searched to identify prospective studies up to May 2019. Random-effects meta-analyses and dose-response meta-analysis were conducted, involving twenty-nine of 20,083 identified literatures. Meta-analysis showed that midlife underweight, obesity and late-life underweight conferred 1.39-, 1.31- and 1.64-fold excess risk for cognitive impairment and dementia, while late-life overweight and obesity conferred 21% and 25% reduced risk. In dose-response meta-analysis, all cause dementia (ACD), Alzheimer’s disease (AD) and vascular dementia (VaD) risk in midlife was significantly elevated when BMI surpassed 29, 30 and 32 kg/m2. AD risk in late-life was decreased when BMI was under 27 kg/m2, while this protection for VaD was absent when BMI surpassed 39 kg/m2. Higher BMI produced opposite exerted opposite effects on dementia in mid- and late-age population. Firstly reported, a dose-response relationship further supports the guideline from the standpoint of dementia prevention.
•Blood Aβ42, Aβ40 and Aβ ratio using IMR technique have great AD diagnostic values.•Blood T-tau and P-tau 181 were increased from controls to aMCI to AD patients.•Blood NfL were increased from ...controls to aMCI patients to AD patients.•Blood platelet AβPPr were decreased from controls to aMCI patients to AD patients.
The development of blood-based biomarkers of Alzheimer’s disease (AD) pathology as tools for screening the general population is essential, but persists controversies. We aimed to evaluate the effects of AD core pathological biomarkers on blood, and systematical searched Embase, PubMed and Cochrane for eligible studies. Biomarker performance was rated by random-effects meta-analysis based on the ratio of means method and multivariable-adjusted effect estimates. Finally, 150 articles were included, which demonstrated T-tau (average ratio: 1.25–1.62), P-tau 181 (1.36–2.16) and NfL (1.24–1.86) were increased, and AβPPr (0.65−0.88) were decreased from controls to amnestic mild cognitive impairment (aMCI) to AD. Furthermore, Aβ42, Aβ42/Aβ40 ratio and P-tau 217 using ultrasensitive platforms also had great diagnostic accuracy from controls to aMCI to AD. Consequently, significantly changes of blood AD core biomarkers were verified in comparison between AD, aMCI and control, supporting biomarkers were strongly valid in identifying AD and aMCI, which provides a new prospect of AD early diagnosis and progressive monitoring. This study is registered with PROSPERO, number CRD42020191927.
Although prostate cancer is clinically manageable during several stages of progression, survival is severely compromised once cells invade and metastasize to distant organs. Comprehending the ...pathobiology of invasion is required for developing efficacious targeted therapies against metastasis. Based on bioinformatics data, we predicted an association of melanoma differentiation-associated gene-9 syntenin, or syndecan binding protein (SDCBP) in prostate cancer progression. Using tissue samples from various Gleason stage prostate cancer patients with adjacent normal tissue, a series of normal prostate and prostate cancer cell lines (with differing tumorigenic/metastatic properties),
-manipulated variants (including loss-of-function and gain-of-function cell lines), and CRISPR/Cas9 stable MDA-9/Syntenin knockout cells, we now confirm the relevance of and dependence on MDA-9/syntenin in prostate cancer invasion. MDA-9/Syntenin physically interacted with insulin-like growth factor-1 receptor following treatment with insulin-like growth factor binding protein-2 (IGFBP2), regulating downstream signaling processes that enabled STAT3 phosphorylation. This activation enhanced expression of MMP2 and MMP9, two established enzymes that positively regulate invasion. In addition, MDA-9/syntenin-mediated upregulation of proangiogenic factors including IGFBP2, IL6, IL8, and VEGFA also facilitated migration of prostate cancer cells. Collectively, our results draw attention to MDA-9/Syntenin as a positive regulator of prostate cancer metastasis, and the potential application of targeting this molecule to inhibit invasion and metastasis in prostate cancer and potentially other cancers.
This study provides new mechanistic insight into the proinvasive role of MDA-9/Syntenin in prostate cancer and has potential for therapeutic application to prevent prostate cancer metastasis.
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Objectives
The amyloid/tau/neurodegeneration (ATN) framework has conceptualized the Alzheimer's disease (AD) continuum as a continuum of disease with evidence of amyloid‐related pathologies ...independent of clinical manifestation. Based on this framework, it is necessary to reveal the distribution and risk factors of AD continuum in the cognitively intact population among different cohorts and races, including the northern Chinese Han population.
Methods
This study classified cognitively intact Chinese Alzheimer's Biomarker and LifestylE (CABLE) participants through the AT(N) scheme. Gaussian mixture models were used to identify the cutoff values of cerebrospinal fluid biomarkers, which distinguished AD continuum ( A + T−N−, A + T + N−, A + T−N + and A + T + N +) from 1,005 participants (mean age 61 years; 40% female). Multivariable logistic regressions and Cochran–Armitage trend tests were used to test neuropsychological performance and risk factors for AD continuum.
Results
Approximately one‐third of individuals (33.7%) belonged to the AD continuum. Four potential modifiable risk factors, including hypertension, thyroid diseases, social isolation, and minimal depression symptoms, were identified for the AD continuum (OR ranging 1.68–6.90). A trend toward higher prevalence of the AD continuum was associated with a larger number of risk factors (p for trend <0.0001). The risk of AD continuum increased by approximately twofold for each additional modifiable risk factor (OR 1.9, 95% CI 1.65–2.24, p < 0.0001).
Interpretation
This study revealed the distribution and potential risk factors of the AD continuum in a cognitively intact Han population in northern China, which filled the gap in the area about the performance of the AT(N) framework in the Asian population. ANN NEUROL 2022;92:439–450
•WMHs conferred a 14 % elevated risk of cognitive impairment and ACD.•WMHs increased both AD risk and VaD risk.•Periventricular WMH were related with increased risk of ACD.•The dose-response analysis ...showed a nonlinear association between WMHs and ACD.
White matter hyperintensities of presumed vascular origin (WMH) are one of the imaging features of cerebral small vessel disease. Controversies persist about the effects of WMH on cognitive dysfunction. This meta-analysis aimed to identify the associations of WMH with risks of cognitive impairment and dementia.
We searched PubMed, EMBASE and Cochrane Library for prospective studies. Primary analyses of cognitive dysfunction and sub-analyses of specific outcomes and study characteristics were conducted using random-effect models.
Thirty-six prospective studies with 19,040 participants were included. WMH at baseline conferred a 14 % elevated risk of cognitive impairment and all-cause dementia (ACD). WMH also conferred 25 % elevated risk of Alzheimer’s disease and 73 % elevated risk of vascular dementia. Risk effects of high-grade WMH and continually increasing WMH (in volume or severity) on ACD were revealed. Periventricular WMH conferred a 1.51-fold excess risk for dementia.
WMH were associated with increased risk of cognitive dysfunction and could become a neuroimaging indicator of dementia.
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