Inhibition of CXCR4: A perspective on miracle fruit seed for Alzheimer's disease treatment.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its causes are currently diverse and not fully understood. In a previous study, we discovered that short-term treatment with miracle fruit seed (MFS) had a therapeutic effect on AD model mice, however, the precise mechanism behind this effect remains unclear. In this research, we aimed to establish the efficacy and safety of long-term use of MFS in AD model mice. A variety of cytokines and chemokines have been implicated in the development of AD. Previous studies have validated a correlation between the expression levels of C-X-C chemokine receptor type 4 (CXCR4) and disease severity in AD. In this research, we observed an upregulation of CXCR4 expression 1n hippocampal tissues in the AD model group, which was then reversed after MFS treatment. Moreover, CXCR4 knockout resulted in improved cognitive function in AD model mice, and MFS showed the ability to regulate CXCR4 expression. Finally, our findings indicate that CXCR4 knockout and long-term MFS treatment produce comparable effects in treating AD model mice. In conclusion, this research demonstrates that therapeutic efficacy and safety of long-term use in AD model mice. MFS treatment and the subsequent reduction of CXCR4 expression exhibit a neuroprotective role in the brain, highlighting their potential as therapeutic targets for AD.

From Liquid to Solid-State Batteries: Li-Rich Mn-Based Layered Oxides as Emerging Cathodes with High Energy Density.

Li-rich Mn-based (LRMO) cathode materials have attracted widespread attention due to their high specific capacity, energy density, and cost-effectiveness. However, challenges such as poor cycling stability, voltage deca,y and oxygen escape limit their commercial application in liquid Li-ion batteries. Consequently, there is a growing interest in the development of safe and resilient all-solid-state batteries (ASSBs), driven by their remarkable safety features and superior energy density. ASSBs based on LRMO cathodes offer distinct advantages over conventional liquid Li-ion batteries, including long-term cycle stability, thermal and wider electrochemical windows stability, as well as the prevention of transition metal dissolution. This review aims to recapitulate the challenges and fundamental understanding associated with the application of LRMO cathodes in ASSBs. Additionally, it proposes the mechanisms of interfacial mechanical and chemical instability, introduces noteworthy strategies to enhance oxygen redox reversibility, enhances high-voltage interfacial stability, and optimizes Li+ transfer kinetics. Furthermore, it suggests potential research approaches to facilitate the large-scale implementation of LRMO cathodes in ASSBs.

A multidimensional nomogram combining clinical factors and imaging features to predict 1-year recurrence of low back pain with or without radicular pain after spinal manipulation/mobilization.

BACKGROUND: In this retrospective study, we aimed to develop a nomogram to predict recurrence during a 1-year period of spinal manipulation/mobilization (SM/M) in patients with low back pain (LBP) with greater pain intensity, more severe comorbid conditions, or a neuropathic component. METHODS: A total of 786 consecutive patients with LBP treated with SM/M as primary therapy were divided into training (n = 545) and validation (n = 241) sets. Cox regression analyses were used to assess the relative value of clinical factors and lumbar magnetic resonance imaging features associated with recurrence during the 1-year period. Predictors of recurrence with significant differences were used to construct a nomogram in the training set. We evaluated the performance of the model on the training and validation sets to determine its discriminative ability, calibration, and clinical utility. The prognostic value of the nomogram for predicting recurrence was assessed using Kaplan-Meier analysis and time-dependent receiver operating characteristic analyses. RESULTS: A nomogram comprising hospitalization time, previous history of LBP, disease duration, lumbar range of motion, lower extremity tendon reflex, muscle strength, ratio of herniation to uncompressed dural sac area, and Pfirrmann classification was established for recurrence during a 1-year period after SM/M in patients with LBP. Favorable calibration and discrimination were observed in the nomogram training and validation sets (C-index 0.753 and 0.779, respectively). Decision curve analysis confirmed the clinical utility of the nomogram. Over a 1-year period, the nomogram showed satisfactory performance in predicting recurrence in LBP after SM/M. CONCLUSION: We established and validated a novel nomogram that can accurately predict a patient's risk of LBP recurrence following SM/M. This realistic prognostic model may aid doctors and therapists in their decision-making process and strategy optimization for non-surgical treatment of LBP using SM/M.

[Investigation and analysis of imported medicinal materials at Chinese border ports].

Imported medicinal materials are an important part of Chinese medicinal resources. To be specific, about 10% of the around 600 commonly used Chinese medicinal materials are from abroad, and the introduction of foreign medicinal materials has promoted the development of Chinese medicine. Amid the advancement of reform and opening up and the "Belt and Road" Initiative, major headway has been made in the cross-border trade in China, bringing opportunities for the import of medicinal materials from border ports. However, for a long time, there is a lack of systematic investigation on the types of exotic medicinal materials at border ports. In the fourth national census of traditional Chinese medicine resources, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, together with several organizations, investigated the nearly 40 border ports, Chinese medicinal material markets, and border trade markets in 6 provinces/autonomous regions in China for the first time and recorded the types, sources, circulation, and the transaction characteristics of imported medicinal materials. Moreover, they invited experts to identify the origins of the collected 237 medicinal materials. In addition, the status quo and the problems of the medicinal materials were summarized. This study is expected to lay a basis for clarifying the market and origins of imported medicinal materials as well as the scientific research on and supervision of them.

NMR Analysis of Lipid Oxidation in Flaxseed Oil-in-Water Emulsions.

The formation of linolenic (Ln) and linoleic (L) acyl oxidation products during storage of flaxseed oil (FO)-in-water emulsions was monitored using proton nuclear magnetic resonance (1H NMR) spectroscopy, as well as chemical analytical methods and gas chromatography. Emulsions containing 10% FO and 1% Tween 60 were prepared by homogenization and then stored at 37 °C in the dark for 21 days under accelerated oxidation conditions (500 µmol ferrous sulfate). The induction time of the emulsions, after which rapid lipid oxidation was first observed, was 5-7 days, as shown by increases in peroxide values and hydroperoxide concentrations determined by NMR spectroscopy. Analysis of the hexanal and propanal concentrations during storage by HS-SPME-GC indicated that the oxidation of Ln and L acyls in the emulsions occurred simultaneously. The oxidation products originating from the Ln and L acyls were monitored using 1H NMR spectroscopy throughout the oxidation process. These results also showed that the Ln and L acyls oxidized simultaneously, and isomers of hydroperoxy-cyclic hydroperoxides (HCPs), Z,E-conjugated dienic hydroperoxides (ZECDHPs), and E,E-conjugated dienic hydroperoxides (EECDHPs) were the major primary oxidation products. Aldehydes were observed after 7 days, which was taken to be the start of the propagation stage, with the formation of a significant amount of oxygenated α, ß-unsaturated aldehydes (OαßUAs). Based on the concentrations of hydroperoxides originating from the Ln and L acyls, our results suggested that the loss rate of L acyls was parallel to that of Ln acyls. This result was consistent with Ln acyls adopting a tighter packing at the oil-water interface in the emulsions than L acyls. This hypothesis was supported by the NMR relaxation time data. A good correlation between the isomer concentrations of ZECDHPs and HCPs in Ln acyls and between ZECDHPs and EECDHPs in L acyls was shown, with the mole ratios between them being 1.2 and 1.1, respectively. Droplet size and microstructure analyses showed that droplet aggregation occurred from 11 days onwards, which was attributed to polar oxidation products located at the oil droplet surfaces promoting coalescence. Zeta-potential measurements indicated that the droplets became more negative during storage, which was attributed to the accumulation of anionic reaction products at the droplet surfaces.

Miracle fruit seed as a potential supplement for the treatment of learning and memory disorders in Alzheimer's disease.

Currently, the treatment of Alzheimer's disease (AD) is still at the stage of symptomatic treatment due to lack of effective drugs. The research on miracle fruit seeds (MFSs) has focused on lipid-lowering and antidiabetic effects, but no therapeutic effects have been reported in AD. The purpose of this study was to provide data resources and a potential drug for treatment of AD. An AD mouse model was established and treated with MFSs for 1 month. The Morris water maze test was used to assess learning memory function in mice. Nissl staining was used to demonstrate histopathological changes. MFSs were found to have therapeutic implications in the AD mouse model, as evidenced by improved learning memory function and an increase in surviving neurons. To explore the mechanism of MFSs in treating AD, network pharmacological approaches, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking studies were carried out. Based on the network pharmacology strategy, 74 components from MFS corresponded to 293 targets related to the AD pathology. Among these targets, AKT1, MAPK3, ESR1, PPARG, PTGS2, EGFR, PPARA, CNR1, ABCB1, and MAPT were identified as the core targets. According to the relevant number of core targets, cis-8-octadecenoic acid, cis-10-octadecenoic acid, 2-dodecenal, and tetradecane are likely to be highly correlated with MFS for AD. Enrichment analysis indicated the common targets mainly enriched in AD and the neurodegeneration-multiple disease signaling pathway. The molecular docking predictions showed that MFSs were stably bound to core targets, specifically AKT1, EGFR, ESR1, PPARA, and PPARG. MFSs may play a therapeutic role in AD by affecting the insulin signaling pathway and the Wnt pathway. The findings of this study provide potential possibilities and drug candidates for the treatment of AD.

Research progress of the CXCR4 mechanism in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative brain disease with complex clinical manifestations and pathogeneses such as abnormal deposition of beta-amyloid protein and inflammation caused by the excessive activation of microglia. CXC motif chemokine receptor type 4 (CXCR4) is a type of G protein-coupled receptor that binds to CXC motif ligand 12 (CXCL12) to activate downstream signaling pathways, such as the Janus kinase/signal transducer and activator of transcription and the renin-angiotensin system (Ras)/RAF proto-oncogene serine (Raf)/mitogen-activated protein kinase/extracellular-regulated protein kinase; most of these signaling pathways are involved in inflammatory responses. CXCR4 is highly expressed in the microglia and astrocytes; this might be one of the important causes of inflammation caused by microglia and astrocytes. In this review, we summarize the mechanism and therapeutics of AD, the structures of CXCR4 and the CXCL12 ligand, and the mechanisms of CXCR4/CXCL12 that are involved in the occurrence and development of AD. The possible treatment of AD through microglia and astrocytes is also discussed, with the aim of providing a new method for the treatment of AD.

Whether it is safe to start anticoagulation after intracranial hemorrhage within 2 weeks: A systematic review and meta-analysis.

Whether restarting anticoagulation (RA) treatment after intracranial hemorrhage (ICH) is still controversial. We performed a systematic review and meta-analysis to summarize the relationship between anticoagulation after ICH with the recurrence of hemorrhagic events, ischemic events, and long-term mortality. Medline, Embase, and the Cochrane Central Register of Controlled Trials, from inception to November 2020. We searched the published medical literature to ensure cohort studies involving ICH associated with anticoagulation in adults. Primary outcomes were long-term mortality, hemorrhagic events, and ischemic events (myocardial infarction, pulmonary embolism, ischemic stroke, or systemic embolization). We concluded seven retrospective cohorts, including 1876 intracranial hemorrhage patients with indications of anticoagulation. The ratio of the anticoagulant restart was 35.3% (664n). RA was associated with a significantly lower incidence of recurrent ischemic events (pooled odds ratio [OR] 0.29, 95% confidence interval [CI] 0.19% to 0.45%, p = 0.97) and death events (pooled OR 0.56, 95% CI 0.40%-0.79%, p = 0.27). There is no evidence that early recovery of anticoagulation (within 2 weeks or 1 month) is associated with the occurrence of hemorrhagic events (within 2 weeks: pooled OR 0.80, 95% CI 0.3-2.12, p = 0.52 vs. within 1 month: pooled OR 1.14, 95% CI 0.77-1.68, p = 0.82). Based on these, recovery of anticoagulation after ICH is beneficial for long-term mortality and recurrence of ischemic events. The meta-analysis showed a resumption of oral anticoagulation within 2 weeks or 1 month in patients who had a cerebral hemorrhage was beneficial and did not increase the risk of hemorrhagic events and reduced the occurrence of ischemic and fatal endpoint events.

Analysis of the potential and mechanism of Ginkgo biloba in the treatment of Alzheimer's disease based on network pharmacology.

Objective: Study the principle and possible mechanism of Ginkgo biloba in the treatment of Alzheimer's disease (AD) which is based on network pharmacology. Methods: The potential targets of active ingredients of Ginkgo biloba were collected by Traditional Chinese Medicine Integrated Database platform (TCMSP). TCMSP is a pharmacological system for drug discovery from Chinese herbal medicine. The disease targets of AD were searched and collected by the database of gene-disease associations (DisGeNET) and literature. The obtained targets were standardized by the UniProt database. STING network platform and Cytoscape were used to construct protein-protein interaction network (PPI) of the key targets. According to Materscape, we clarify the possible mechanism of action including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis. Results: The compound-target network contains 27 active ingredients, 191 related targets, 18 key targets, including PLAU, HMOX1, TNF, INSR, MPO, MAOB, IGF2, IL1B, ESR1, BCL2, ACHE, BAX, GSK3B, PPARG, SLC2A4, NOS3, CASP3, VEGFA. GO enrichment analysis has got a total of 640 GO items, including 609 biological process (BP) items (95.1%), 16 molecular function (MF) items (2.5%) and 15 cellular component (CC) items (2.4%). After KEGG enrichment, 44 pathways were obtained. Conclusion: Through the construction of "component-target-pathway", GO biological function and KEGG pathway enrichment analysis were performed on core targets, and the possibility of Ginkgo biloba for the treatment of AD was explored from multiple targets and pathways, which provided a new approach for multi-target treatment.

Discoveries of the specific expression of lncRNAs and mRNAs in hippocampus of rats after traumatic brain injury.

Objects: Explore the relationship between the neural function deficit and the changes of lncRNA and mRNA in hippocampus after traumatic brain injury (TBI) in rats. Methods: Twenty male rats weighted 200-240 grams were randomly divided into sham group and TBI group. Neurologic severity score (NSS) was performed after operation, and the hippocampus of rats was collected for long non-coding RNAs (lncRNAs), mRNAs microarray detection, real-time quantitative PCR Detecting System (Q-PCR), western blot (WB) detection, and serum biochemical detection. Results: The NSS score of the TBI group was significantly higher than the sham group. Compared with the sham group, 270 lncRNAs changed in the TBI group, of which 224 were up-regulated and 46 were down-regulated. Among up-regulated lncRNAs, mRNAs were distributed in upstream of 22 lncRNAs, downstream of 17 lncRNAs, overlapping regions of 48 lncRNAs, and antisense chains of 21 lncRNAs. Among down-regulated lncRNAs, mRNAs were distributed in upstream of 6 lncRNAs, downstream of 3 lncRNAs, overlapping regions of 10 lncRNAs, and antisense chains of 8 lncRNAs. Compared with the sham group, 1054 mRNA changed in the TBI group, of which 921 mRNA were up-regulated and 133 mRNA were down-regulated. The expression changes of ENSRNOT000063054, ENSRNOT000052790, ENSRNOT00000054410, ENSRNOT000063242, and ENSRNOT000069411 IncRNA regulate the expression of Top2a, RT1-CE11, Papss2, Stk32a, and Grid2 gene. Conclusion: The present study detected the differential expression of lncRNAs and mRNAs in hippocampi of rats subjected to TBI, and discussed their relation, primarily.

New lignanamides and alkaloids from Chelidonium majus and their anti-inflammation activity.

Two new lignanamides, majusamides A and B (1 and 2), and two new alkaloids, chelidoniumine (3) and tetrahydrocoptisine N-oxide (4), together with six known hydroxycinnamic acid amides (HCCA) were isolated from the 75% ethanol extract of Chelidonium majus through the silica gel, Sephadex LH-20, MCI, ODS column chromatography, and semi-HPLC. Their structures were determined on the basis of spectroscopic data and physico-chemical methods. The absolute configurations of 1-3 were determined by electronic circular dichroism (ECD) calculations. The anti-inflammatory activities of all the isolates on the NO production in lipopolysaccharide (LPS)-induced macrophages were evaluated. Compounds 7 and 9 exhibited moderate inhibitory activity with IC50 values of 25.3 ±â€¯0.5 and 23.5 ±â€¯1.7 µM, respectively.

Four new compounds from the roots of Euphorbia ebracteolata and their inhibitory effect on LPS-induced NO production.

Three new diterpenoids, ebractenoids O~Q (1-3), and a new phenolic glucoside, γ-pyrone-3-O-ß-d-(6-galloyl)-glucopyranoside (4), together with 6 known compounds, were isolated from the 95% ethanol extract of the roots of Euphorbia ebracteolata, and their structures were elucidated on the basis of spectroscopic data. The absolute configurations of 1-3 were determined by electronic circular dichroism (ECD) calculations. The inhibitory effects of all the isolates with exception of compounds 8 and 10 on the NO production in lipopolysaccharide (LPS)-induced macrophages were evaluated. All of them exhibited significant inhibitory activity.