Systematic review and meta-analysis: Impact of depression on prognosis in inflammatory bowel disease.

BACKGROUND AND AIM: Depression is highly prevalent in patients with inflammatory bowel disease (IBD), which may affect the prognosis of IBD. This aimed to investigate the impact of depression on prognosis in IBD. METHODS: A systematic literature search was performed in four databases (Medline, Embase, Web of Science, and PsycINFO) up to December 31, 2023. Studies were included if they investigated the impact of depression on prognosis in IBD. The primary outcome was flare in IBD, and secondary outcomes were hospitalization, readmission, emergency visits, surgery, and escalation of medical therapy. Relative risks (RRs) were utilized to estimate the risk in each of the above prognostic indicators. RESULTS: Fourteen cohort and 10 case-control studies matched our entry criteria, comprising 630 408 patients with IBD. Twenty-two of included studies were considered to have a low risk of bias. Depression was found to significantly increase the risk of flare (RR = 1.37, 95% CI 1.16-1.63), hospitalization (RR = 1.11, 95% CI 1.00-1.23), readmission (RR = 1.32, 95% CI 1.04-1.67), emergency visits (RR = 1.33, 95% CI 1.12-1.59), surgery (1.38, 95% CI 1.08-1.76), and escalation of medical therapy (RR = 1.38, 95% CI 1.13-1.69) in IBD. Of note, patients with depression in ulcerative colitis had significant differences in readmission (RR = 1.38, 95% CI 1.19-1.60) and escalation of medical therapy (RR = 1.78, 95% CI 1.55-2.04). Additionally, the association was observed in patients with Crohn's disease in terms of flare (RR = 1.47, 95% CI 1.08-2.01) and hospitalization (RR = 1.20, 95% CI 1.03-1.40). CONCLUSIONS: Current evidence suggested that depression could significantly increase the risk of poor prognosis worsening in patients with IBD. However, the association varied in IBD subtypes.

Uncovering the effect and mechanism of Jiawei Xiaoyao Wan in treating breast cancer complicated with depression based on network pharmacology and experimental analysis.

BACKGROUND: Depression is a clinically common co-morbidity in breast cancer cases that brings negative outcomes on quality of life and potentially survival. Jiawei Xiaoyao Wan (JXW) is widely used in treating breast cancer and depressive disorder, but its potential pharmacological mechanisms remain elusive. PURPOSE: We aimed to explore the dual therapeutic effects and mechanisms of JXW acting on breast cancer complicated with depression (BCCD) by network pharmacology and in vivo experimental verification. METHODS: The chemical constituents of JXW were characterized using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-Q-TOF/MS). The targets related to constituents of JXW were predicted by the TCMSP and Swiss Target Prediction databases, and targets of breast cancer and depression were screened by the GeneCards and OMIM databases. Gene Ontology annotation and KEGG enrichment analysis were performed with the DAVID database. Ultimately, a BCCD mouse model induced by chronic restraint stress (CRS) was used to explore therapeutic effects and mechanisms of JXW against BCCD. The efficacy of JXW in the treatment of BCCD was evaluated based on behavioral tests, tumor volume and weight, and pathological examination. Additionally, the underlying mechanisms were explored by measuring the levels of neurotransmitter and inflammatory factors, as well as detecting the expression of genes or proteins associated with candidate targets and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway through RT-PCR, western blotting, and immunohistochemistry. RESULTS: Totals of 108 components were identified in JXW using LC-Q-TOF/MS. By network pharmacology analysis, 714 compound targets of JXW, 2114 breast cancer targets, 1122 depression targets, and 98 overlapping proteins were obtained. PPI network and KEGG analysis implied that TP53, ESR1, VEGFA, AKT1, IL6, TNF, EGFR and the JAK/STAT pathway might be the potential targets of JXW in treating BCCD. In vivo experiments indicated that JXW significantly ameliorated depressive symptoms and tumor progression in BCCD mice. Further mechanistic studies showed that JXW could reduce the levels of inflammatory factors, increase 5-HT level, and regulate mRNA expression levels of TP53, VEGFA, AKT1, IL6, TNF, and EGFR targets. Moreover, the expression levels of proteins related to the JAK2/STAT3 signaling pathway in BCCD mice were effectively regulated by JXW. CONCLUSION: JXW exerts dual therapeutic effects in a BCCD mouse via multiple targets. The underlying mechanisms might be associated with regulating the levels of neurotransmitter and inflammatory factors; more importantly, the JAK2/STAT3 pathway plays a significant role in this process.

Exploring the mechanism of Si-Ni-San against depression by UPLC-Q-TOF-MS/MS integrated with network pharmacology: experimental research.

Background: Depression is becoming an urgent mental health problem. Si-Ni-San has been widely used to treat depression, yet its underlying pharmacological mechanism is poorly understood. Thus, we aim to explore the antidepressant mechanism of Si-Ni-San by chemical analysis and in-silico methods. Methods: Compounds in Si-Ni-San were determined by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Then, bioactive compounds were obtained from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform and SwissADME, and the potential targets of which were acquired from SwissTargetPrediction. Depression-related targets were collected from GeneCards. The intersection between compound-related targets and depression-related targets were screened out, and the overlapped targets were further performed protein-protein interaction, biological functional and pathway enrichment analysis. Finally, networks of Si-Ni-San against depression were constructed and visualized by Cytoscape. Results: One hundred nineteen compounds in Si-Ni-San were determined, of which 24 bioactive compounds were obtained. Then, 137 overlapped targets of Si-Ni-San against depression were collected. AKT1, PIK3R1, PIK3CA, mTOR, MAPK1 and MAPK8 were the key targets. Furthermore, PI3K-Akt signalling pathway, serotonergic synapse, MAPK signalling pathway and neurotrophin signalling pathway were involved in the antidepressant mechanism of Si-Ni-San. It showed that components like sinensetin, hesperetin, liquiritigenin, naringenin, quercetin, albiflorin and paeoniflorin were the mainly key active compounds for the antidepressant effect of Si-Ni-San. Conclusions: This study demonstrated the key components, key targets and potential pharmacological mechanisms of Si-Ni-San against depression. These results indicate that Si-Ni-San is a promising therapeutic approach for treatment of depression, and may provide evidence for the research and development of drugs for treating depression.

SNHG25 promotes colorectal cancer metastasis by regulating MMP2.

LncRNA has been shown to play an important role in tumors, but the functions of most lncRNAs in colorectal cancer is not clear. By analyzing the transcriptome data of tumor tissues and adjacent tissues, we identified the lncRNA profiles that were abnormally expressed in colorectal cancer and selected the abnormally highly expressed lncRNA SNHG25 for further study. The functional assays showed that after knocking down SNHG25, the metastatic ability of colorectal cancer cells was significantly reduced. Western blot and immunofluorescence assays showed that inhibiting SNHG25 would affect the expression of Vimentin and E-Cadherin. In terms of mechanism, the results of RNA pull down assays, RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays showed that SNHG25 could promote MMP2 expression by adsorbing miR-296-3p. In addition, chromatin immunoprecipitation (ChIP) assays and promoter luciferase reporter assays revealed that PAX5 could activate the transcription of SNHG25 in colorectal cancer cells. Our study proved that SNHG25 acts a pro-metastasis role in colorectal cancer, enriching the theory of the functions of lncRNA in colorectal cancer.

Cobalt-Catalyzed Chemoselective Reduction of N-Heteroaryl Ketones with N,N-Dimethylformamide as a Hydride Source.

A method for chemoselective reduction of 2-pyridyl ketones and related N-heteroaryl compounds catalyzed by cobalt stearate using DMF as a hydride source is developed. The ketone substrate is activated by chelation with cobalt, which makes the present method highly chemoselective. A possible reaction mechanism is proposed on the basis of control experiments.

Superlithiation Performance of Pyridinium Polymerized Ionic Liquids with Fast Li+ Diffusion Kinetics as Anode Materials for Lithium-Ion Battery.

Polymerized ionic liquids (PILs) with super ion diffusion kinetics have aroused considerable attention in rechargeable batteries, which are very promising to solve the problem of the slow ion diffusion kinetics in organic electrode materials. Theoretically, PILs incorporated redox groups are very suitable as anode materials to realize "superlithiation" performance, achieving high lithium storage capacity. In this study, redox pyridinium-based PILs (PILs-Py-400) have been synthesized through trimerization reactions by pyridinium ionic liquids with cyano groups under an appropriate temperature (400 °C). The positively charged skeleton, extended conjugated system, abundant micropores, and amorphous structure for PILs-Py-400 can boost the utilization efficiency of redox sites. A high capacity of 1643 mAh g-1 at 0.1 A g-1 (96.7% of the theoretical capacity) has been obtained, indicating intriguing 13 Li+ redox reactions in per repeating unit of one pyridinium ring, one triazine ring, and one methylene. Moreover, PILs-Py-400 exhibit excellent cycling stability with a capacity of around 1100 mAh g-1 at 1.0 A g-1 after 500 cycles, and the capacity retention is 92.2%.

[Anti-depression mechanism of Zuojin Pills:based on UHPLC-TOF-MS, network pharmacology, and experimental verification].

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.

Explainable Deep Learning-Assisted Photochromic Sensor for ß-Lactam Antibiotic Identification.

Photochromic sensors have the advantages of diverse isomers for multi-analysis, providing more sensing information and possessing more recognition units and more sensitivity to external stimulations, but they present enormous complexity with various stimulations as well. Deep learning (DL) algorithms contribute a huge advantage at analyzing nonlinear and multidimensional data, but they suffer from nontransparent inner networks, "black-boxes". In this work, we employed the explainable DL approach to process and explicate photochromic sensing. Spirooxazine metallic complexes were adopted to prepare a multi-state analysis array for ß-Lactams identification and quantitation. A dataset of 2520 unduplicated fluorescence intensity images was collected for convolutional neural network (CNN) operation. The method clearly discriminated six ß-Lactams with 97.98% prediction accuracy and allowed rapid quantification with a concentration range from 1 to 100 mg/L. The photochromic sensing mechanism was verified via molecular simulation and class activation mapping, which explicated how the CNN model assesses the importance of photochromic sensor states and makes a discrimination decision. The explainable DL-assisted analysis method establishes an end-to-end strategy to ascertain and verify the complicated sensing mechanism for device optimization and even new scientific discovery.

Pd/MIL-100(Fe) as hydrogen activator for FeIII/FeII cycle: Fenton removal of sulfamethazine.

Masses of iron sludge generated from engineering practice of classic Fenton reaction constraints its further promotion. Accelerating the FeIII/FeII cycle may be conducive to reducing the initial ferrous slat dosage and the final iron sludge. Based on the reduction of Pd/MIL-100(Fe)-activated hydrogen, an improved Fenton system named MHACF-MIL-100(Fe) was developed at ambient temperature and pressure. 97.8% of sulfamethazine, the target pollutant in this work, could be degraded in 5 min under the conditions of 20 mM H2O2, 25 µM ferrous chloride, initial pH 3.0, 2 g·L-1 composite catalyst Pd/MIL-100(Fe) and hydrogen gas 60 mL·min-1. Combining density functional theory (DFT) calculation and intermediate detection, the degradation of this antibiotic was inferred to start from the cleavage of N-S bond. The catalytic of Pd/MIL-100(Fe), demonstrated by the removal efficiency of SMT and the catalyst morphology, remained intact after six reaction cycles. The present study provides an insight into the promotion of Fenton reaction.

[Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics].

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

A case study on the bearing characteristics of a bottom uplift pile in a layered foundation.

The bottom uplift pile, which has been applied in practical projects, has the following advantages: the pile body is not easy to crack, good bearing characteristics, and small displacement of the pile top. Based on the bearing capacity test of foundation piles in the third stage expansion project of Lanzhou Zhongchuan International Airport, the upper part pile of the self-balancing test method was used to simulate the bottom uplift pile, and the anchor piles in the anchor pile method were regarded as normal uplift piles. The bearing characteristics of the bottom uplift pile in a layered foundation were studied by comparing these two kinds of piles. The results show that under the same displacement of the pile top, the ultimate uplift bearing capacity of the bottom uplift pile can be more than twice that of the normal uplift pile because of the fully exerted frictional resistance of the soil at the bottom of the pile, the Poisson effect of the pile body and the avoidance of the influence of pile body deformation on the pile top displacement. The maximum axial force of the bottom uplift pile appears at the bottom of the pile and gradually decreases from the bottom to the top, which is opposite to that of the normal uplift pile. The properties and thickness of the soil layers around the pile have a great influence on the distribution curves of the frictional resistance along the pile length of the two kinds of uplift piles. With changing soil layer conditions, the distribution curve may be a "parabola", a "straight line" or a "double line". The soil property plays a decisive role in the frictional resistance, which may cause softening. The influence of the pile diameter on the ultimate uplift bearing capacity is greater than that of the pile length, while the elastic modulus of the pile has little influence.

Insight into the nature of the noncovalent interactions of furan, pyridine, and pyrazine with AtX.

CONTEXT: The σ-hole, counterintuitive σ-hole, and lone pair-π interaction complexes formed between three heterocyclic compounds (C4H4O, C5H5N, and C4H4N2) and AtX (X = F, Cl, and Br) have been investigated with the MP2/aug-cc-pVTZ. The intensity of three noncovalent interactions formed by different heterocyclic compounds was compared, and the properties of these three noncovalent interactions were discussed. SAPT analysis shows that the electrostatic energy is dominant to the stronger interactions in the σ-hole and counterintuitive σ-hole complexes, while the dispersion energy is the main force responsible for the weaker interactions in the lone pair-π complexes. NBO analysis has also been employed. METHODS: All the structures were optimized at the MP2/aug-cc-pVTZ (aug-cc-pVTZ-pp for Br to account for relativistic effects) level using the Gaussian 03W package (Gaussian, Inc., Wallingford, CT, USA). The basis bet superposition error (BSSE) is corrected using counterpoise method proposed by Boys and Bernardi. The NBO population analysis was carried out. The molecular electrostatic surface potentials of monomers were calculated by WFA-SAS program package. The interaction energies of the three types complexes were decomposed by using the symmetric adaptive perturbation theory SAPT of the open source ab initio electronic structure software package psi 4.0.0-beta5.

Intrinsic Analysis of Thermally Activated Delayed Fluorescence (TADF) for Ag(I) Complex Based on the Path Integral Approach: Origin of the Effective Spin-Flipping Channel and Vibrational Spin-Orbit Coupling Effect.

In order to design new Ag(I)-based materials for thermally activated delayed fluorescence (TADF), it is vital to develop a detailed understanding of the current best performing materials. The quantitative predictions of the photophysical processes of the Ag(dmp)(P2-nCB) TADF complex are calculated using time-dependent density functional theory (TD-DFT) combined with the path integral approach for dynamics including the Herzberg-Teller effects. All calculated results are in good agreement with the experimentally available data, demonstrating the validity of our applied theoretical approach. Analysis of ETS-NOCV (extended transition state natural orbital for chemical valence) shows that there is a weak bond interaction dominated by electrostatic interactions and accompanied by some covalent components between Ag(I) and dmp ligands due to the introduction of the strongly electron-donating negatively charged P2-nCB ligand, thus giving a small energy separation between the lowest singlet S1 and triplet T1 states of ΔE(S1 - T1) ≈ 532 cm-1. The SOC strongly depends on the geometrical alteration caused by the molecular "promotion" vibrations. Our study has revealed that a few "promotion" vibrational modes, that is, ω46 and ω227, effectively induce the strong SOC between S1 and T1 and speed up the reverse intersystem crossing (RISC) process dramatically. The computed kRISC value is 1.19 × 107 s-1 for the solid phase at 300 K, which are about 5 orders of magnitude larger than the mean phosphorescence rate, kP = 9.56 × 102 s-1, and it is also far larger than ISC k0ISC = 7.84 × 102 s-1 rates from T1 to S0. The S1 state thus can be an efficient thermal repopulation from the T1 state by the RISC pathway. Finally, we also note that the diabatic vibration coupling triplet pair T1/T2 will also be important for efficient and practical RISC. Our investigation will be of great utility toward designing and improving the Ag(I)-based TADF complexes.

[Pharmacokinetic interaction of Jiaotai Pills and Fluoxetine in rats with CUMS-induced depression].

A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.

Potential Anti-Depressive Effects and Mechanisms of Zhi-Zi Hou-Po Decoction Using Behavioral Despair Tests Combined With in Vitro Approaches.

Zhi-Zi Hou-Po Decoction (ZHD) has been widely used in the treatment of depression for centuries. This study aimed to investigate the antidepressant effects of the water extract of ZHD (ZHD-WE) and ethanol extract of ZHD (ZHD-EE) using behavioral despair tests in mice, and to further explore the neuroprotective effects in a PC12 cell injury model induced by corticosterone (CORT). Mice were divided into a control group (normal saline), ZHD-WE groups (4, 8, and 16 g kg-1), ZHD-EE groups (4, 8, and 16 g kg-1) and the fluoxetine group (20 mg kg-1). The forced swimming test (FST) and tail suspension test (TST) were used to screen the antidepressant effects of ZHD-WE and ZHD-EE after oral administration for seven consecutive days. The level of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined by ELISA. The MTT, lactate dehydrogenase (LDH) and flow cytometry analysis were performed to elucidate the neuroprotective effect of ZHD-EE on a PC12 cell injury model. Additionally, the mRNA and proteins expression of apoptotic molecules Bax, Bcl-2 and BDNF were detected by RT-PCR and western blot assay. It showed that ZHD-EE at concentrations of 8 and 16 g kg-1 significantly decreased the immobility time in the TST and FST, and increased the BDNF levels in the hippocampus. While ZHD-WE at concentrations of 4, 8, and 16 g kg-1 had no significant effect on the immobility time in the TST, and only the 16 g kg-1 of extract group significantly decreased the immobility time in the FST. In vitro, the obtained results showed that PC12 cells pre-incubated with ZHD-EE at concentrations of 100 and 400 µg ml-1 improved cell viability, decreased LDH release, and reduced apoptosis rate of PC12 cells. Moreover, ZHD-EE significantly increased the mRNA and proteins expression of Bcl-2 and BDNF, while decreased the mRNA and protein expression of Bax. ZHD-EE significantly improved despair-like behavior in mice, and its mechanism may be related to BDNF upregulation in the hippocampus. This study also showed that ZHD-EE had a protective effect on CORT-induced injury in PC12 cells by upregulating the expression of BDNF and restoring Bcl-2/Bax balance.

Biomarkers of Metabolomics in Inflammatory Bowel Disease and Damp-Heat Syndrome: A Preliminary Study.

Aims: This study aims to investigate the potential biomarkers of inflammatory bowel disease (IBD) and IBD with damp-heat syndrome (IBD-DH) by metabolomics. Methods: Plasma and urine samples were collected from 15 healthy controls and 30 IBD patients, including 15 IBD-DH and 15 IBD with spleen deficiency syndrome (IBD-SD), which was coded as SF8G and SF70 according to the International Classification of Diseases Eleventh Revision (ICD-11) issued by World Health Organization. Pseudotargeted metabolomics method was used based on ultra-high-performance liquid chromatography-high-resolution mass spectrometry and triple-quadrupole mass spectrometry. Results: Under the condition of false discovery rate (FDR) < 0.05, variable importance projection (VIP) > 1.0, and fold change (FC) > 1.5 or < 2/3, we found 57 plasma differential metabolites and 20 urinary differential metabolites in IBD. Then, with area under the curve (AUC) ≥ 0.85 and FC ≥ 2 or ≤ 0.3, 11 potential biomarkers were identified, such as acylcarnitine (ACar 20:4, ACar 18:1, and ACar 20:3), 3-indoleacetic acid, hippuric acid, and dehydroepiandrosterone sulfate, which is related to intestinal microbiota and immune response. However, less obvious differences were observed in IBD-DH when compared with IBD-SD. Under the condition of FDR < 0.2, VIP >1.0, and FC > 1.5 or < 2/3, we identified 16 plasma differential metabolites. In urine samples, IBD-DH and IBD-SD had the same metabolite pattern. With AUC ≥ 0.80, 7 differential plasma metabolites, mainly glycerophospholipids, were identified in IBD-DH. Kyoto Encyclopedia of Genes and Genomes analysis indicated that metabolic pathways, such as citrate cycle and amino acids metabolism, were mainly responsible for the distinction between IBD and healthy controls, whereas glycerophospholipid metabolism perturbation was not only a manifestation of IBD but also an important pathway to distinguish two subtypes defined by traditional medicine, IBD-DH and IBD-SD. Conclusion: In this study, we found that several metabolites of aromatic acids and lipid derivatives could act as potential biomarkers to discriminate IBD from healthy controls. Glycerophospholipids metabolites might be used to differentiate IBD-DH from IBD-SD.

Salidroside ameliorates orthopedic surgery-induced cognitive dysfunction by activating adenosine 5'-monophosphate-activated protein kinase signaling in mice.

Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Salidroside, a plant-derived compound, has gained increased attention as a treatment for various neurological diseases and particularly as a modifier of microglia-mediated neuroinflammation. However, the effect of salidroside on orthopedic surgery-induced cognitive dysfunction and the underlying mechanisms are largely unknown. Here, we found that salidroside greatly attenuated cognitive impairment in mice after orthopedic surgery. Neuroinflammation in the mouse hippocampus was also attenuated by salidroside. Meanwhile, salidroside treatment induced a switch in microglial polarization to the anti-inflammatory phenotype. In vitro, salidroside suppressed the expression of proinflammatory cytokines and induced a switch in microglial phenotype to the anti-inflammatory phenotype. Mechanistically, molecular docking studies revealed the potential AMPK activation activity of salidroside. And salidroside did up-regulated the AMPK pathway proteins. Moreover, AMPK antagonist abolished the effects of salidroside in vivo and in vitro. Taken together, our results demonstrated that salidroside effectively suppressed PND by suppressing microglia-mediated neuroinflammation through activating AMPK pathway, and it might be a novel therapeutic approach for PND.

ACSL4 promotes colorectal cancer and is a potential therapeutic target of emodin.

BACKGROUND: Colorectal cancer (CRC) is an important death-related disease in the world and new therapeutic strategies are urgently needed to reduce mortality. Several studies have demonstrated that emodin, the main ingredient of Rheum palmatum, fights cancer but its potential anti-tumor effect on CRC is still unknown. PURPOSE: The present study is aimed to explore the potential anti-tumor effects of emodin against CRC and the underlying molecular mechanism. METHODS: CRC-related datasets were screened according to filter criteria in the GEO database and TCGA database. By using screened differentially expressed genes, GO, KEGG and survival analysis were carried out. The expressions of ACSL4, VEGFR1, and VEGFR2 were examined by immunohistochemistry and western blot. Then, pcDNA-ACSL4, pcDNA-VEGFR1, and pcDNA-VEGFR2 were used to overexpress ACSL4, VEGFR1, and VEGFR2, while ACSL4 siRNA was used to silence ACSL4 expression in HCT116 cells. CCK-8 assay and transwell migration assay were used to detect the cell proliferation and invasion. A docking simulation assay and an MST assay were performed to explore the potential mode of emodin binding to ACSL4. The HCT116 cells and CRC mouse model were established to investigate the effects of emodin on CRC. RESULTS: The ACSL4, VEGFR1, and VEGFR2 expression were upregulated in CRC tissues and ACSL4 was associated with a shorter survival time in CRC patients. ACSL4 downregulation reduced cell proliferation and invasion, while ACSL4 exhibited a positive correlation with the levels of VEGFR1, VEGFR2, and VEGF. In HCT116 cells, emodin reduced cell proliferation and invasion by inhibiting ACSL4, VEGFR1, and VEGFR2 expression and VEGF secretion. Docking simulation and MST assay confirmed that emodin can directly bind to ACSL4 target. Moreover, ACSL4 overexpression abolished the inhibitory effect of emodin on VEGF secretion and VEGFR1 and VEGFR2 expression, but VEGFR1 and VEGFR2 overexpression did not affect the inhibitory effect of emodin on ACSL4 expression and VEGF secretion. Furthermore, emodin reduced the mortality and tumorigenesis of CRC mice and reduced ACSL4, VEGFR1, VEGFR2 expression, and VEGF content. CONCLUSION: Our findings indicate that emodin inhibits proliferation and invasion of CRC cells and reduces VEGF secretion and VEGFR1 and VEGFR2 expression by inhibiting ACSL4. This emodin-induced pathway offers insights into the molecular mechanism of its antitumor effect and provides a potential therapeutic strategy for CRC.

Evidence for Anticancer Effects of Chinese Medicine Monomers on Colorectal Cancer.

Colorectal cancer is one of the most commonly occurring cancers worldwide. Although clinical reports have indicated the anticancer effects of Chinese herbal medicine, the multiple underlying molecular and biochemical mechanisms of action remain to be fully characterized. Chinese medicine (CM) monomers, which are the active components of CM, serve as the material basis of the functional mechanisms of CM. The aim of this review is to summarize the current experimental evidence from in vitro, in vivo, and clinical studies for the effects of CM monomers in colorectal cancer prevention and treatment, providing some useful references for future research.

Ratiometric Fluorescence Detection of Mg2+ Based on Regulating Crown-Ether Modified Annihilators for Triplet-Triplet Annihilation Upconversion.

Detection of magnesium ion has been of great significance considering its critical physiological activities. Herein, we report ratiometric fluorescence detection of Mg2+ with high sensitivity and selectivity based on triplet-triplet annihilation (TTA) upconversion for the first time. Crown-ether functionalized anthracene derivatives were synthesized, which bifunctionally acted as not only annihilators to construct TTA upconversion systems but also the recognition probes for Mg2+ based on the photoinduced electron transfer (PET) mechanism. Their photophysical properties with the absence and presence of Mg2+ were comprehensively studied. It was found that solvents strongly influenced the photophysical properties and Mg2+-responsiveness. TTA upconversion systems with PtOEP as the sensitizer were further established and investigated. It turned out PtOEP/9-AEC in DCM exhibited an excellent linear relationship (R2 = 0.9979) between the intensity ratio (the integrated upconverted luminescence intensity (IUC) over the integrated downshifted phosphorescence intensity (IPL), IUC/IPL) and the concentration of Mg2+ under the excitation of 532 nm with a limit of detection value of 2.52 µM and a high selectivity to Mg2+. This work opened a new perspective of designs and applications of TTA-upconversion-based ratiometric fluorescence for ion detection.