GABAergic interneurons in the hippocampal CA1 mediate contextual fear generalization in PTSD rats.

Fear overgeneralization is widely accepted as a pathogenic marker of post-traumatic stress disorder (PTSD). Recently, GABAergic interneurons have been regarded as key players in the regulation of fear memory. The role of hippocampal GABAergic interneurons in contextual fear generalization of PTSD remains incompletely understood. In the present study, we established a rat model of PTSD with inescapable foot shocks (IFS) and observed the loss of GABAergic interneuron phenotype in the hippocampal cornu ammonis-1 (CA1) subfield. To determine whether the loss of GABAergic interneuron phenotype was associated with fear generalization in PTSD rats, we used adeno-associated virus (AAV) to reduce the expression of GAD67 in CA1 and observed its effect on fear generalization. The results showed that the reduction of GAD67 in CA1 enhanced contextual fear generalization in rats. We investigated whether the PERK pathway was involved in the GABAergic interneuron injury. Increased expression of p-PERK, CHOP, and Caspase12 in GABAergic interneurons of PTSD rats was observed. Then, we used salubrinal, an endoplasmic reticulum stress inhibitor, to modulate the PERK pathway. The salubrinal treatment significantly protected the GABAergic interneurons and relieved fear generalization in PTSD rats. In addition, the results showed that salubrinal down-regulated the expression of CHOP and Caspase12 in GABAergic interneurons of PTSD rats. In conclusion, this study provided evidence that the loss of GABAergic interneuron phenotype in CA1 may contribute to contextual fear generalization in PTSD. The PERK pathway is involved in the GABAergic interneuron injury of PTSD rats and modulating it can protect GABAergic interneurons and constrain contextual fear generalization.

Hippocampal parvalbumin and perineuronal nets: Possible involvement in anxiety-like behavior in rats.

The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67-immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα-immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV-immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN-coated PV-positive interneurons in CA1. The number of PSD95-positive excitatory synaptic puncta on the soma of PNN-free PV-positive interneurons was significantly higher than that of PNN-coated PV-positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell-type-specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV-PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety-like behavior.

The impact of lactating Hu sheep's dietary protein levels on lactation performance, progeny growth and rumen development.

This study aimed to investigate whether lactating Hu sheep's dietary protein levels could generate dynamic effects on the performance of their offspring. Twelve ewes with similar parity were fed iso-energy diets which contained different protein levels (P1: 9.82%, P2: 10.99%) (n = 6), and the corresponding offspring were divided into SP1 and SP2 (n = 12). At 60 days, half of the lambs were harvested for further study: the carcass weight (p = 0.043) and dressing percentage (p = 0.004) in the SP2 group were significantly higher than SP1. The acetic acid (p = 0.007), propionic acid (p = 0.003), butyric acid (p < 0.001) and volatile fatty acids (p < 0.001) in rumen fluid of SP2 were significantly lower than SP1. The expression of MCT2 (p = 0.024), ACSS1 (p = 0.039) and NHE3 (p = 0.006) in the rumen of SP2 was lower than SP1, while the HMGCS1 (p = 0.026), HMGCR (p = 0.024) and Na+/K+-ATPase (p = 0.020) was higher than SP1. The three dominant phyla in the rumen are Bacteroidetes, Proteobacteria and Firmicutes. The membrane transport, amino acid metabolism and carbohydrate metabolism of SP1 were relatively enhanced, the replication and repair function of SP2 was relatively enhanced. To sum up, the increase of dietary protein level significantly increased the carcass weight and dressing percentage of offspring and had significant effects on rumen volatile fatty acids, acetic acid activation and cholesterol synthesis related genes. HIGHLIGHTSIn the early feeding period, the difference in ADG of lambs was mainly caused by the sucking effect.The increase in dietary protein level of ewes significantly increased the carcass weight and dressing percentage of offspring.The dietary protein level of ewes significantly affected the volatile fatty acids (VFAs) and genes related to acetic acid activation and cholesterol synthesis in the rumen of their offspring.The membrane transport, amino acid metabolism and carbohydrate metabolism of the offspring of ewes fed with a low protein diet were relatively enhanced.The replication and repair function of the offspring of ewes fed with a high protein diet was relatively strengthened.

Exploration of the Core Pathways and Potential Targets of Luteolin Treatment on Late-Onset Depression Based on Cerebrospinal Fluid Proteomics.

Cognitive deficiency is one of the fundamental characteristics of late-onset depression (LOD). Luteolin (LUT) possesses antidepressant, anti-aging, and neuroprotective properties, which can dramatically enhance cognition. The altered composition of cerebrospinal fluid (CSF), which is involved in neuronal plasticity and neurogenesis, directly reflects the physio-pathological status of the central nervous system. It is not well known whether the effect of LUT on LOD is in association with a changed CSF composition. Therefore, this study first established a rat model of LOD and then tested the therapeutic effects of LUT using several behavioral approaches. A gene set enrichment analysis (GSEA) was used to evaluate the CSF proteomics data for KEGG pathway enrichment and Gene Ontology annotation. We combined network pharmacology and differentially expressed proteins to screen for key GSEA-KEGG pathways as well as potential targets for LUT therapy for LOD. Molecular docking was adopted to verify the affinity and binding activity of LUT to these potential targets. The outcomes demonstrated that LUT improved the cognitive and depression-like behaviors in LOD rats. LUT may exert therapeutic effects on LOD through the axon guidance pathway. Five axon guidance molecules-EFNA5, EPHB4, EPHA4, SEMA7A, and NTNG-as well as UNC5B, L1CAM, and DCC, may be candidates for the LUT treatment of LOD.

Prenatal Diagnosis of Fetal Oral Masses by Ultrasound Combined With Magnetic Resonance Imaging.

OBJECTIVES: To analyze the imaging manifestations of common fetal oral masses by ultrasound combined with magnetic resonance imaging (MRI) and to discuss their differential diagnoses. METHODS: A retrospective study of 6 fetuses with oral masses was performed at a tertiary referral center. The imaging features of prenatal ultrasonography and MRI in the diagnosis of fetal oral masses were analyzed. RESULTS: Histopathological examination and/or postpartum ultrasound revealed lymphangioma malformation in 2 fetuses, and mucosal retention cyst, mature teratoma, immature teratoma, and cranial meningocele in 1 fetus, respectively. The teratoma had a characteristic sonographic appearance. In our study, the 4 cases of cystic masses did not have an abnormal vessel architecture. Supplemental MRI revealed a mass effect at the level of the hypopharynx, and in 2 cases with polyhydramnios, the mass obstructed the fetuses' upper airway. Thus, ex-utero intrapartum therapy surgery was performed to secure the newborn's airway. CONCLUSIONS: Oral fetal tumors represent rare congenital malformations. This study shows that a prenatal diagnosis of oral masses is feasible by ultrasound examination. MRI can further confirm the results of ultrasonography and clearly show the relationship between the mass and the hypopharynx. Ultrasonography combined with MRI could, to a large extent, facilitate early detection and appropriate treatment and improve outcome.

Cerebrospinal fluid proteomics reveal potential protein targets of JiaWeiSiNiSan in preventing chronic psychological stress damage.

CONTEXT: Chinese herbal formula JiaWeiSiNiSan (JWSNS) has been widely used to prevent stress-induced neuropsychiatric ailments in clinics and proven to have therapeutic anti-stress effects on rats. However, the mechanism remains unclear. OBJECTIVE: Based on the proteomics of cerebrospinal fluid (CSF), this study explores the possible mechanism and target proteins of JiaWeiSiNiSan raising stress resilience and preventing stress damage. MATERIALS AND METHODS: A 6-week Chronic Unpredictable Mild Stress (CUMS) model was applied on adult Wistar male rats to observe the effects of JWSNS on improving mental stress resilience. Tandem Mass Tag (TMT) proteomics and bioinformatics analysis were used to screen and analyze differentially expressed proteins (DEPs) in CSF. Parallel Reaction Monitoring (PRM) was used to validate target DEPs. RESULTS: Significantly decreased sucrose preference, locomotion activity level and accuracy of T-maze, as well as increased immobility time, were observed in CUMS rats compared to CON rats while JWSNS improved above depression-like behaviours. The quantitative proteomics and bioinformatics analysis showed that JWSNS decreased the expression of Rps4x, HSP90AA1, Rps12, Uba1, Rsp14, Tuba1b in CUMS rats CSF (p < 0.05, FDR < 0.5). Immunofluorescence results showed that the number of BrdU/DCX positive cells (p < 0.01) and the relative number of neurons (p < 0.01) in the hippocampus dentate gyrus (DG) of the JSWNS group significantly increased, compared with the CUMS group. CONCLUSIONS: JWSNS could increase mental stress resilience and prevent stress damage by regulating proteins in CSF. This study provides a scientific basis for further study on Chinese formulas preventing mental illness.

Integrated biomarker for type 2 diabetes mellitus and impaired fasting glucose based on metabolomics analysis using ultra-high performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry.

RATIONALE: The prevalence of type 2 diabetes mellitus (T2DM) is increasing but its early diagnosis in high risk populations remains challenging using only fasting blood glucose (FBG) or hemoglobin A1c measurements. It is, therefore, important to search for an integrated biomarker for early diagnosis by determining metabolites associated with the progression of the disease. METHODS: We recruited 149 participants (51 T2DM patients, 50 individuals with impaired fasting glucose (IFG) and 48 normal glucose tolerance subjects). Their serum samples were analyzed based on a metabolomics approach using ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS). The changes in metabolites were profiled and evaluated using univariate and multivariate analyses. Furthermore, a biomarker model was established and the potential biomarkers were evaluated using binary logistic regression analysis and receiver operating characteristic analysis with AUC (area under the curve). Pathway analysis of differential metabolites was performed to reveal the important biological information. RESULTS: Thirty-eight differential metabolites were identified as significantly associated with T2DM patients and 23 differential metabolites with IFG individuals, mainly amino acids, carnitines, and phospholipids. By evaluating 17 potential biomarkers, we defined a novel integrated biomarker consisting of 2-acetolactate, 2-hydroxy-2,4-pentadienoate, L-arabinose and L-glutamine. The AUCs of the integrated biomarker with IFG and T2DM patients were 0.874 and 0.994, respectively, which showed a superior diagnostic performance. The levels of 2-acetolactate and 2-hydroxy-2,4-pentadienoate were strongly positively correlated with FBG, while L-glutamine and L-arabinose were strongly negatively associated with FBG. After pathway analysis, it was suggested that the majority of the influenced metabolic pathways associated with diabetes referred to amino acid metabolism. CONCLUSIONS: The integrated biomarker could diagnose IFG and T2DM with a superior diagnostic performance. This finding provides support for novel biomarkers in the diagnosis and treatment of diabetes.

Metabolic profile of alkaloids in Rhizoma Coptidis in rat plasma, urine and feces after oral administration using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

RATIONALE: Rhizoma Coptidis (RC) has been used to treat diabetes, pertussis, bacillary dysentery, sore throat, eczema, and aphtha for thousands of years. Alkaloids are the major components in RC, and its curative effect is achieved by oral administration. However, information on its composition in vivo is weak. METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS) was used to analyze the major active components and their metabolites in rat plasma, urine and feces after oral administration of RC extract. RESULTS: A total of 96 compounds including 8 prototype compounds and 88 metabolites were identified, and hydroxylation, reduction, demethylenation, demethylation, dehydrogenation, sulfation, glucuronidation and methylation were the major metabolic pathways. CONCLUSIONS: This study analyzed metabolic processes of the major active components in RC in vivo, which provided important information for its active composition and in vivo mechanism research. Meanwhile, metabolic profile studies on representative compounds provided valuable reference materials to elucidate the full-scale metabolites of RC.

Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis.

BACKGROUND: We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. METHODS: Four databases, the Cochrane Library, EMBASE, PubMed and Scopus were selected. A random effect model and a fixed effect model were applied to the results of forest plot analyses to determine the standardized mean difference (SMD) and 95% confidence interval (95% CI) for each metabolite. The SMD for every metabolite was then converted into an odds ratio to create an metabolite biomarker profile. RESULTS: Twenty-four independent studies reported data from 14,131 healthy individuals and 3499 patients with T2DM, and 14 included studies reported 4844 healthy controls and a total of 2139 pre-diabetes patients. In the serum and plasma of patients with T2DM, compared with the healthy participants, the concentrations of valine, leucine, isoleucine, proline, tyrosine, lysine and glutamate were higher and that of glycine was lower. The concentrations of isoleucine, alanine, proline, glutamate, palmitic acid, 2-aminoadipic acid and lysine were higher and those of glycine, serine, and citrulline were lower in prediabetic patients. Metabolite biomarkers of T2DM and pre-diabetes revealed that the levels of alanine, glutamate and palmitic acid (C16:0) were significantly different in T2DM and pre-diabetes. CONCLUSIONS: Quantified multiple metabolite biomarkers may reflect the different status of pre-diabetes and T2DM, and could provide an important reference for clinical diagnosis and treatment of pre-diabetes and T2DM.

Antidepressant pathways of the Chinese herb jiaweisinisan through genetic ontology analysis.

Active compounds and corresponding targets of the traditional Chinese herb, jiaweisinisan, were obtained from systems pharmacological database and placed into ClueGO for gene ontology analysis. The targets of depression were obtained from the Online Mendelian Inheritance in Man, the Therapeutic Target Database, and the Pharmacogenomics Knowledge Base. Compound-target and target-pathway networks were constructed using Cytoscape, and then their topological parameters were analyzed. The targets of jiaweisinisan and depression were mapped to pathways, thereby constructing antidepressant pathways of jiaweisinisan. It was found that jiaweisinisan has 82 different active compounds and 306 relevant potential targets. Also, 107 unrepeatable targets related to depression were found. In all, 26 common targets were found to be the direct anti-depression targets of jiaweisinisan and 9 pathways of jiaweisinisan related to depression were divided into three modules (synaptic transmission, cell apoptosis, and immune-inflammatory). The jiaweisinisan formula was found to have synergistic antidepressant effects due to aspects of its herb composition and the active compounds therein, giving rise to potential targets and signaling pathways related to depression. Its antidepressant mechanisms were found to mainly involve the regulation of synaptic transmission, cell apoptosis, and immune-mediated inflammation.

Population pharmacokinetics of high-dose methotrexate in Chinese pediatric patients with medulloblastoma.

Methotrexate (MTX) pharmacokinetics has substantial inter-individual variability and toxicity. In children with medulloblastoma treated with high-dose methotrexate (HD-MTX), the pharmacokinetic properties of methotrexate have not been established. A total of 660 serum samples from 105 pediatric patients with medulloblastoma were included in a population pharmacokinetic (PPK) analysis of methotrexate by using the nonlinear mixed-effects modeling method. The basic one-compartment population pharmacokinetic model was established by NONMEM software and the first-order conditional estimation (FOCE) method, and the final covariate model was obtained by the stepwise regression method. Weight (WT), creatinine clearance (CrCL), and whether the treatment was combined with dexamethasone (DEX) were covariates that had significant effects on the clearance rate (CL) of the model. The pharmacokinetic equation of CL in the final covariate model was as follows: CLi = 9.23× (1 + 0.0005× (θCrCL -105.78)) × (1 + 0.0017× (θWT -16)) × eηcl,i (L/h), IF (θDEX ) CLi = 1.19× CLi (L/h). The estimation accuracy of all pharmacokinetic parameters were acceptable (relative standard error < 14.74%). The goodness-of-fit diagram and bootstrap tests indicated that the final PPK model was stable with acceptable predictive ability. The PPK model may be useful for determining personalized medication levels in pediatric medulloblastoma patients undergoing HD-MTX therapy.

[Study on mechanism of Guilu Erxianjiao in treatment of post-traumatic stress disorder based on network pharmacology].

The aim of this paper was to predict the multi-compound, multi-target and multi-pathway mechanism of Guilu Erxianjiao in treating post-traumatic stress disorder(PTSD) based on network pharmacology. Active compounds and corresponding targets of Guilu Erxianjiao were obtained from TCMSP, BATMAN-TCM, Chemistry and DrugBank database, and known therapeutic targets of PTSD were obtained from OMIM, TTD and DisGeNET Database. The protein interaction network of compound-disease was then built by combining with the STRING Database. Topological parameters of the network were analyzed by Cytoscape 3.6.0 to get key active compounds and their targets. The GO biological process analysis and KEGG pathway analysis of the key targets were conducted. Based on the results of KEGG, the "compound-target-pathway" network was built by Cytoscape 3.6.0 and the results were verified by SystemsDock online molecular docking tool. The prediction results showed that there were 67 active compounds and 420 targets for Guilu Erxianjiao, and 206 known PTSD-related therapeutic targets. Besides, 66 targets, 58 terms and 22 pathways were obtained from Cytoscape 3.6.0 topological parameters analysis, GO biological process analysis, and KEGG pathway analysis, respectively. Molecular docking results showed that both target with the maximum degree value and common targets of PTSD and Guilu Erxianjiao in the pathway can be effectively combined with their corresponding active compounds through molecular docking. The results suggested that Guilu Erxianjiao could exert anti-PTSD effect by regulating synaptic plasticity, anti-apoptotic, anti-inflammatory and promoting fear memory extinction through pathways such as LTP, PI3 K/Akt/mTOR, TNF, serotonergic synapse and dopaminergic synapse. This study provides a theoretical basis for further elucidating pharmacological mechanisms of Guilu Erxianjiao in treating PTSD.

Effect of Toddalia asiatica extract combined with miR-483 on proliferation, apoptosis and inflammatory factors expression of osteoarthritis chondrocyte.

This study aims to investigate the effect of Toddalia asiatica extract combined with miR-483 on osteoarthritis chondrocyte proliferation and apoptosis and expression of inflammatory factors. Osteoarthritis chondrocytes were treated with Toddalia asiatica extract. Osteoarthritis chondrocytes were transfected with anti-miR-483 or miR-483 and Toddalia asiatica extract was applied. The levels of TNF-α, IL-6, IL-10 were determined by ELISA. Cell proliferation and cloning were evaluated by MTT and cloning experiment. Cell apoptosis was determined by flow cytometry. P21 and caspase-3 protein expression were analyzed by Western blot. The expression of miR-483 was detected by qRT-PCR. The application of Toddalia asiatica extract or inhibition of miR-483 significantly increased the cell survival rate, cloning count and IL-10 level of osteoarthritis chondrocytes, and significantly reduced the apoptosis rate, levels of P21, Caspase-3, TNF-α IL-6 and miR-483 expression level of osteoarthritis chondrocytes (p<0.05). Overexpression of miR-483 could reverse the promotion effect of Toddalia asiatica extract on osteoarthritis chondrocytes proliferation, clone formation and IL-10 level, as well as reserve the inhibition effect of Toddalia asiatica extract on osteoarthritis chondrocyte apoptosis and levels of P21, caspase-3, TNF-α, IL-6. The combination of Toddalia asiatica extract and miR-483 can promote the proliferation of osteoarthritis chondrocytes and inhibit apoptosis and expression of inflammatory factors.

Dissipation and Migration of Pyrethroids in Auricularia polytricha Mont. from Cultivation to Postharvest Processing and Dietary Risk.

In order to ensure raw consumption safety the dissipation behavior, migration, postharvest processing, and dietary risk assessment of five pyrethroids in mushroom (Auricularia polytricha Mont.) cultivated under Chinese greenhouse-field conditions. Half-lives (t1/2) of pyrethroids in fruiting body and substrate samples were 3.10-5.26 and 17.46-40.06 d, respectively. Fenpropathrin dissipated rapidly in fruiting bodies (t1/2 3.10 d); bifenthrin had the longest t1/2. At harvest, pyrethroid residues in A. polytricha (except fenpropathrin) were above the respective maximum residue limits (MRLs). Some migration of lambda-cyhalothrin was observed in the substrate-fruit body system. In postharvest-processing, sun-drying and soaking reduced pyrethroid residues by 25-83%. We therefore recommend that consumers soak these mushrooms in 0.5% NaHCO3 at 50 °C for 90 min. Pyrethroids exhibit a particularly low PF value of 0.08-0.13%, resulting in a negligible exposure risk upon mushroom consumption. This study provides guidance for the safe application of pyrethroids to edible fungi, and for the establishment of MRLs in mushrooms to reduce pesticide exposure in humans.

[Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing].

With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.

Multi-Residue Analysis of Pesticide Residues in Crude Pollens by UPLC-MS/MS.

A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% to 136% with relative standard deviations (RSDs) below 30%. Of the 54 targeted compounds, 19 pesticides were detected. The major detection rates of each compound were 77.1% for carbendazim, 58.3% for fenpropathrin, 56.3% for chlorpyrifos, 50.0% for fluvalinate, 31.3% for chlorbenzuron, and 29.2% for triadimefon in crude pollen samples. The maximum values of each pesticide were 4516 ng/g for carbendazim, 162.8 ng/g for fenpropathrin, 176.6 ng/g for chlorpyrifos, 316.2 ng/g for fluvalinate, 437.2 ng/g for chlorbenzuron, 79.00 ng/g for triadimefon, and so on. This study provides basis for the research on the risks to honeybee health.

RECK overexpression reduces invasive ability in ameloblastoma cells.

BACKGROUND: Ameloblastoma is a frequent odontogenic neoplasm characterized by local invasiveness and high risk of recurrence. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a tumor suppressor that inhibits metastasis and angiogenesis. The aim of this study was to investigate effects of RECK overexpression on invasive potential in ameloblastoma cells. METHODS: Lentiviral vectors containing human RECK gene were created and subsequently stably transfected into immortalized ameloblastoma cell line hTERT(+) -AM. Functional characteristics of hTERT(+) -AM cells with stable RECK overexpression included proliferation, migration, invasion, and regulation of matrix metalloproteinases (MMP)-2, MMP-9 measured by zymography or commercially available assays. RESULTS: The stable and higher expression of RECK mRNA and protein (P < 0.01) was detected in RECK-transfected hTERT(+) -AM cells. RECK overexpression caused a decrease in migration and invasion (P < 0.01) for hTERT(+) -AM cells and a decrease in activity of MMP-2, MMP-9 (P < 0.01). Proliferation was not affected by RECK overexpression (P > 0.05). CONCLUSIONS: Overexpression of RECK gene significantly inhibited cell invasive ability of hTERT(+) -AM cells, suggesting RECK may be a new target for ameloblastoma treatment.

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

BACKGROUND: Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies. AIMS: In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective. RESULTS: The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions. CONCLUSIONS: Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.

Paeoniflorin exerts anti-PTSD effects in adult rats by modulating hippocampus and amygdala histone acetylation modifications in response to early life stress.

Early life stress (ELS) can cause long-term changes by epigenetic factors, especially histone acetylation modification, playing a crucial role, affect normal cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood. It has been found that paeoniflorin (PF) can cross the blood-brain barrier to exert anti-PTSD effects on adult PTSD rats. However, whether PF can alleviate the harmful effects caused by ELS in adulthood has not yet been reported. Therefore, to explore the relationship between ELS and PTSD susceptibility in adulthood and its mechanism, in this study, SPS was used as a stressor of ELS, and the mathematical tool Z-normalization was employed as an evaluation criterion of behavioral resilience susceptibility. To investigate the regulatory mechanism of PF on histone acetylation in the hippocampus and amygdala of ELS rats in adulthood, using changes in HATs/HDACs as the entry point, meanwhile, the epigenetic marks (H3K9 and H4K12) in the key brain regions of ELS (hippocampus and amygdala) were evaluated, and the effects of PF on behavioral representation and PTSD susceptibility were observed. This study found that ELS lead to a series of PTSD-like behaviors in adulthood and caused imbalance of HATs/HDACs ratio in the hippocampus and amygdala, which confirms that ELS is an important risk factor for the development of PTSD in adulthood. In addition, paeoniflorin may improve ELS-induced PTSD-like behaviors and reduce the susceptibility of ELS rats to develop PTSD in adulthood by modulating the HATs/HDACs ratio in the hippocampus and amygdala.

Assessing the risk of concurrent mycoplasma pneumoniae pneumonia in children with tracheobronchial tuberculosis: retrospective study.

Objective: This study aimed to create a predictive model based on machine learning to identify the risk for tracheobronchial tuberculosis (TBTB) occurring alongside Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: Clinical data from 212 pediatric patients were examined in this retrospective analysis. This cohort included 42 individuals diagnosed with TBTB and Mycoplasma pneumoniae pneumonia (combined group) and 170 patients diagnosed with lobar pneumonia alone (pneumonia group). Three predictive models, namely XGBoost, decision tree, and logistic regression, were constructed, and their performances were assessed using the receiver's operating characteristic (ROC) curve, precision-recall curve (PR), and decision curve analysis (DCA). The dataset was divided into a 7:3 ratio to test the first and second groups, utilizing them to validate the XGBoost model and to construct the nomogram model. Results: The XGBoost highlighted eight significant signatures, while the decision tree and logistic regression models identified six and five signatures, respectively. The ROC analysis revealed an area under the curve (AUC) of 0.996 for XGBoost, significantly outperforming the other models (p < 0.05). Similarly, the PR curve demonstrated the superior predictive capability of XGBoost. DCA further confirmed that XGBoost offered the highest AIC (43.226), the highest average net benefit (0.764), and the best model fit. Validation efforts confirmed the robustness of the findings, with the validation groups 1 and 2 showing ROC and PR curves with AUC of 0.997, indicating a high net benefit. The nomogram model was shown to possess significant clinical value. Conclusion: Compared to machine learning approaches, the XGBoost model demonstrated superior predictive efficacy in identifying pediatric patients at risk of concurrent TBTB and Mycoplasma pneumoniae pneumonia. The model's identification of critical signatures provides valuable insights into the pathogenesis of these conditions.