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Weinreich Haynes opublikował 1 rok, 8 miesięcy temu
Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4, tnf, il1β), and markers of lipid accumulation (Oil Red O, srbep1) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy.Background To evaluate the efficacy, safeness and cost of ultrasound-guided local lauromacrogol injection (USG-LLI) combined with curettage and hysteroscopy for cesarean scar pregnancy (CSP). Methods This was a retrospective study included 151 CSP patients diagnosed with CSP from June 2017 to December 2019, and treated by USG-LLI (n = 86) or uterine artery embolization (UAE) (n = 65) combined with curettage and hysteroscopy. Clinical data and outcome were analyzed. Results There were no significant differences in basic clinical characteristics in the two groups. Two groups showed the similar success rates. USG-LLI group, compared with UAE group had significantly lower complication rates (9.30 vs. 44.62%), lower total costs (both medical and non-medication cost) (p less then 0.05). Conclusions USG-LLI combined with curettage and hysteroscopy is a feasible method to treat CSP with minimal invasion and high efficacy. Moreover, compared with curettage after UAE, USG-LLI exhibited lower complication rate and required fewer expenses.Background D-dimer is a small protein fragment and high levels of D-dimer have been associated with increased mortality in patients presenting to emergency departments with infection. Previous studies have reported increased levels of D-dimer in COVID-19; however, it is unclear whether an increased D-dimer level provides early warning of poor prognosis. Therefore, this study aimed to assess the usefulness of D-dimer as an early indicator of prognosis in patients with coronavirus disease (COVID-19). Methods We conducted a retrospective study of patients with COVID-19 admitted to Leishenshan Hospital in Wuhan, China, from February 15 to March 30, 2020. The final date of follow-up was April 11, 2020. Results Of the 1,643 patients with COVID-19, 691 had elevated D-dimer levels. Their median age was 65 years. Of the patients with elevated D-dimer levels, 45% had comorbidities, with cardiovascular disease (205 [29.7%]) being the most common. Patients with elevated D-dimer were more likely to require treatment with high-flow oxygen, anticoagulation, antibiotics, and admission to the intensive care unit They were also more likely to have increased interleukin-6, monocytes, and lymphocytes. Patients with elevated D-dimer levels had significantly higher mortality than those with normal or low D-dimer levels. Conclusion In patients with COVID-19, elevated D-dimer was associated with abnormal immunity, underlying disease, increased disease severity, and increased mortality. Taken together, D-dimer may be a marker for the early warning of disease severity and increased risk of death. These findings provide insights into the potential risk of elevated D-dimer in patients with COVID-19.The root of Reynoutria multiflora (Thunb.) Moldenke (syn. Polygonum multiflorum Thunb., HSW) is a distinguished herb that has been popularly used in traditional Chinese medicine (TCM). Evidence of its potential side effect on liver injury has accumulated and received much attention. The objective of this study was to profile the metabolic characteristics of lipids in injured liver of rats induced by HSW and to find out potential lipid biomarkers of toxic consequence. A lipopolysaccharide (LPS)-induced rat model of idiosyncratic drug-induced liver injury (IDILI) was constructed and evident liver injury caused by HSW was confirmed based on the combination of biochemical, morphological, and functional tests. A lipidomics method was developed for the first time to investigate the alteration of lipid metabolism in HSW-induced IDILI rat liver by using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry coupled with multivariate analysis. A total of 202 characterized lipids, including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), phosphatidylinositol (PI), lysophosphatidylinositol (LPI), phosphatidylserine (PS), phosphoglycerols (PG), and ceramide (Cer), were compared among groups of LPS and LPS + HSW. A total of 14 out 26 LPC, 22 out of 47 PC, 19 out of 29 LPE, 16 out of 36 PE, and 10 out of 15 PI species were increased in HSW-treated rat liver, which indicated that HSW may cause liver damage via interfering the phospholipid metabolism. The present work may assist lipid biomarker development of HSW-induced DILI and it also provide new insights into the relationships between phospholipid perturbation and herbal-induced idiosyncratic DILI.Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.Background Several vascular risk factors, including hypertension, diabetes, body mass index, and smoking status are found to be associated with cognitive decline and the risk of Alzheimer’s disease (AD). We aimed to investigate whether an aggregation of vascular risk factors modulates the amplitude of low-frequency fluctuation (ALFF) in patients with mild cognitive impairment (MCI). Methods Forty-three MCI patients and twenty-nine healthy controls (HCs) underwent resting-state functional MRI scans, and spontaneous brain activity was measured by the ALFF technique. The vascular risk profile was represented with the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score, and each group was further divided into high and low risk subgroups. Two-way ANOVA was performed to explore the main effects of diagnosis and vascular risk and their interaction on ALFF. Results The main effect of diagnosis on ALFF was found in left middle temporal gyrus (LMTG) and left superior parietal gyrus (LSPG), and thgregation of vascular risk factors modulates the spontaneous brain activity in MCI patients, and this may serve as a potential imaging mechanism underlying vascular contribution to AD.Face recognition deficits are frequently reported in Alzheimer’s disease (AD) and often attributed to memory impairment. However, it has been hypothesized that failure in identifying familiar people could also be due to deficits in higher-level perceptual processes, since there is evidence showing a reduced inversion effect for faces but not for cars in AD. To address the involvement of these higher processes, we investigated event-related potential (ERP) neural correlates of faces in a patient with AD showing a face recognition deficit. Eight healthy participants were tested as a control group. Participants performed different tasks following the stimulus presentation. In experiment 1, they should indicate whether the stimulus was either a face or a house or a scrambled image. In experiments 2 and 3, they should discriminate between upright and inverted faces (in experiment 2, stimuli were faces with neutral or fearful expressions, while in experiment 3, stimuli were famous or unfamiliar faces). Electrophysiological results reveal that the typical face-specific modulation of the N170 component, which is thought to reflect the structural encoding of faces, was not present in patient MCG, despite being affected by the emotional content of the face implicitly processed by MCG. Conversely, the N400 component, which is thought to reflect the recruitment of the memory trace of the face identity, was found to be implicitly modulated in MCG. These results may identify a possible role for gnosic processes in face recognition deficits in AD and suggest the importance of adopting an integrated approach to the AD diagnosis while considering electrophysiological markers.Objective The study aims to detect the potential relationship between iron deposition and the function of the glymphatic system in the normal aging brain. Methods We recruited 213 healthy participants. We evaluated the function of the glymphatic system using the index for diffusivity along the perivascular space (ALPS-index), assessed iron deposition on quantitative susceptibility mapping (QSM), and analyzed their relationship. Results The mean age of participants was 60.1 ± 7.3, and 107 (50.2%) were female. The mean ALPS-index was 1.4 ± 0.2. The QSM values of the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus, substantia nigra, and dentate nucleus were all related to the ALPS-index (all P less then 0.001). Conclusions The main finding of the current study is that the regional brain iron deposition was related to the function of the glymphatic system. Advances in knowledge We first evaluated the relationship between deposition of brain iron and the dysfunction of the glymphatic system.Synaptic adhesion molecules regulate synapse development through trans-synaptic adhesion and assembly of diverse synaptic proteins. Many synaptic adhesion molecules positively regulate synapse development; some, however, exert negative regulation, although such cases are relatively rare. In addition, synaptic adhesion molecules regulate the amplitude of post-synaptic receptor responses, but whether adhesion molecules can regulate the kinetic properties of post-synaptic receptors remains unclear. Here we report that Clmp, a homophilic adhesion molecule of the Ig domain superfamily that is abundantly expressed in the brain, reaches peak expression at a neonatal stage (week 1) and associates with subunits of AMPA receptors (AMPARs) and kainate receptors (KARs). Clmp deletion in mice increased the frequency and amplitude of AMPAR-mediated miniature excitatory post-synaptic currents (mEPSCs) and the frequency, amplitude, and decay time constant of KAR-mediated mEPSCs in hippocampal CA3 neurons. Clmp deletion had minimal impacts on evoked excitatory synaptic currents at mossy fiber-CA3 synapses but increased extrasynaptic KAR, but not AMPAR, currents, suggesting that Clmp distinctly inhibits AMPAR and KAR responses. Behaviorally, Clmp deletion enhanced novel object recognition and susceptibility to kainate-induced seizures, without affecting contextual or auditory cued fear conditioning or pattern completion-based contextual fear conditioning. These results suggest that Clmp negatively regulates hippocampal excitatory synapse development and AMPAR and KAR responses in the neonatal hippocampal CA3 as well as object recognition and kainate seizure susceptibility in mice.


