[Mechanism of Xueshuantong Injection on bleomycin-induced pulmonary fibrosis in rats based on coagulation cascade pathway].

This study aims to investigate the mechanism of Xueshuantong Injection(XST) on pulmonary fibrosis induced by bleomycin(BLM) in rats based on the coagulation cascade pathway. Sixty SD rats were randomly divided into sham surgery group,model group, pirfenidone(PFD, 50 mg·kg~(-1)) group, and 27, 54, and 81 mg·kg~(-1) XST groups. The rat model of pulmonary fibrosis was established by intratracheal injection of BLM(5 mg·kg~(-1)). After 24 hours, the administration groups were given corresponding drugs, while the sham surgery group and model group were given equal volumes of saline. On the 28th day, samples were collected,and the imaging and collagen fiber changes in the lungs of rats were observed. Immunofluorescence(IF) method was used to detect the expression level of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col-Ⅰ), E-cadherin(E-cad), and vimentin(Vim). Western blot was used to determine the protein expression of α-SMA, Col-Ⅰ, Vim, and E-cad. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of prothrombin fragment(F1 + 2), thrombin-antithrombin complex(TAT), soluble fibrin monomer complex(SFMC), and rat fibrinogen degradation products(FDP) in rat lung tissue. Finally, the mRNA and protein levels of protease activated receptor 1(PAR-1) were detected by RT-qPCR, western blot, and IF. Compared with the model group, the scanning of the lungs of rats receiving XST treatment also exhibited patchy and non-homogeneous shadows, but these shadows were less dense than those in the model group. At the same time, there was a significant decrease in Col-Ⅰ fibers in the lungs of rats, and XST could inhibit epithelial-mesenchymal transition(EMT) and downregulate α-SMA and Col-Ⅰ protein expression. In the aspect of the coagulation system, administration of 81 mg·kg~(-1) XST significantly reduced the levels of SFMC and FDP. Meanwhile, 81 mg·kg~(-1) XST significantly downregulated the mRNA and protein levels of PAR-1. XST has an anti-pulmonary fibrosis effect in rats, and its mechanism may be related to the downregulation of PAR-1 to rebalance the coagulation cascade pathway.

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.

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.

Quercetin reshapes gut microbiota homeostasis and modulates brain metabolic profile to regulate depression-like behaviors induced by CUMS in rats.

Quercetin, an abundant flavonoid compound in plants, is considered a novel antidepressant; however, its mechanisms of action are poorly understood. This study aimed to investigate the therapeutic effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in rats and explore the underlying mechanisms by combining untargeted metabolomics and 16S rRNA sequencing analysis of brain tissue metabolites and gut microbiota. Gut microbiota analysis revealed that at the phylum level, quercetin reduced Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio and enhanced Cyanobacteria. At the genus level, quercetin downregulated 6 and upregulated 14 bacterial species. Metabolomics analysis revealed that quercetin regulated multiple metabolic pathways, including glycolysis/gluconeogenesis, sphingolipid metabolism, the pentose phosphate pathway, and coenzyme A biosynthesis. This modulation leads to improvements in depression-like phenotypes, anxiety-like phenotypes, and cognitive function, highlighting the therapeutic potential of quercetin in treating depression.

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.

GRP94 in cerebrospinal fluid may contribute to a potential biomarker of depression: Based on proteomics.

The present study was designed to investigate potential biomarkers of depression and targets of antidepressants from the perspective of hippocampal endoplasmic reticulum stress (ERS) based on cerebrospinal fluid (CSF) proteomics. Firstly, a six-week depression model was established and treated with fluoxetine (FLX). We found antidepressant-FLX could ameliorate depression-like behaviors and cognition in depressed rats caused by chronic unpredictable mild stress (CUMS). FLX significantly increased neuronal numbers in dentate gyrus (DG) and CA3 regions of hippocampus. CSF proteome data revealed thirty-seven differentially expressed proteins (DEPs) co-regulated by CUMS and FLX, including GRP94 and EIF2α. Results of Gene Oncology (GO) annotation and KEGG pathway enrichment for DEPs mainly included PERK-mediated unfolded protein response, endoplasmic reticulum, and translational initiation. The expression levels of GRP94, p-PERK, p-EIF2α, CHOP and Caspase-12 were increased in hippocampus of CUMS rats, and FLX worked the opposite way. FLX had strong affinity and binding activity with GRP94 protein, and four key proteins on the PERK pathway (PERK, EIF2α, p-EIF2α, CHOP). We proposed that FLX may exert antidepressant effects and neuroprotective action by alleviating excessive activation of the hippocampal PERK pathway and reducing neuronal deficits in depressed rats. PERK, EIF2α, p-EIF2α, and CHOP may be potential targets for antidepressant-FLX. GRP94 in CSF may be a potential biomarker of depression and the therapeutic effects of antidepressants.

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.

Causal relationships between blood lipids and major psychiatric disorders: Univariable and multivariable mendelian randomization analysis.

BACKGROUND: Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate associations of blood lipids with psychiatric disorders. METHODS: Univariable and multivariable models were established for MR analyses. Inverse variance-weighted (IVW) MR was employed as the main approach; weighted median and MR-Egger were used as sensitivity analysis methods. The possibility of violating MR assumptions was evaluated utilizing several sensitivity analyses, including heterogeneity statistics, horizontal pleiotropy statistics, single SNP analysis, leave-one-out analysis and MR-PRESSO analysis. As instrumental variables, we screened 362 independent single-nucleotide polymorphisms (SNP) related to blood lipids from a recent genome-wide association study involving 76,627 individuals of European ancestry, with a genome-wide significance level of p < 5 × 10- 8. Summary-level information for the six psychiatric disorders was extracted from Psychiatric Genomics Consortium and Alzheimer Disease Genetics Consortium. RESULTS: We observed eight significant associations in univariable MR analysis, four of which were corroborated by multivariable MR (MVMR) analysis modified for the other three lipid traits: high-density lipoprotein cholesterol (HDL-C) level with the risk of PTSD (OR = 0.91, 95% CI = 0.85-0.97, p = 0.002) and AD (OR = 0.79, 95% CI = 0.71-0.88, p < 0.001) and triglycerides (TG) level with the risk of MDD (OR = 1.02, 95% CI = 1.003-1.03, p = 0.01) and panic disorder (OR = 0.83, 95% CI = 0.74-0.92, p < 0.001). In addition, four associations were not significant in MVMR analysis after adjustment for three lipid traits: total cholesterol (TC) level with the risk of PTSD, low-density lipoprotein cholesterol (LDL-C) level with the risk of MDD and AD and TG level with the risk of AD. CONCLUSIONS: Our results show that blood lipids and psychiatric disorders may be related in a causal manner. This shows that abnormal blood lipid levels may act as reliable biomarker of psychiatric disorders and as suitable targets for their prevention and treatment.

The Effectiveness and Safety of Exenatide Versus Metformin in Patients with Polycystic Ovary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects women of childbearing age, resulting in reproductive dysfunction, hyperinsulinemia, and obesity. While several drugs are currently approved for use in these patients, their relative effectiveness remains controversial. The purpose of this meta-analysis was to evaluate the reproductive efficacy and safety of exenatide, a glucagon-like peptide-1 receptor agonist, versus metformin, an insulin sensitizer, in the treatment of patients with PCOS. Nine randomized controlled trials (RCTs) were included, comprising 785 PCOS patients, of whom 385 received exenatide and 400 received metformin. Compared with metformin, exenatide was significantly more effective in treating these patients, as demonstrated by increased pregnancy rate (relative risk (RR) = 1.93, 95% confidence interval (CI) 1.28 to 2.92, P = 0.002), greater ovulation rate (RR = 1.41, 95% CI 1.11 to 1.80, P = 0.004), decreased body mass index (mean difference = - 1.72 kg/m2, 95% CI - 2.27 to - 1.18, P = 0.00001), and improved insulin resistance (standard mean difference = - 0.62, 95% CI - 0.91 to - 0.33, P < 0.0001). There was no significant difference in the occurrence of adverse events (gastrointestinal reactions, hypoglycemia, etc.) between the two therapies. However, given the moderate to high quality and possible bias of the included studies, the available evidence is inconclusive. More high-quality studies are needed to assess the effects of exenatide in order to provide stronger evidence for its use in this patient population.

Novel qualitative and quantitative ultrasound markers to facilitate prenatal diagnosis of congenital duodenal obstruction.

OBJECTIVE: Accurate prenatal diagnosis of congenital duodenal obstruction (CDO) is challenging. We aimed to determine new ultrasound metrics for accurate prenatal diagnosis of fetal CDO. METHODS: Data pertaining to 46 fetuses with suspected small intestinal obstruction (26 CDO; 16 high jejunal obstructions) were retrospectively analyzed. Prenatal ultrasonographic features including dilated intestinal length, stomach length, maximum intestinal dilatation, ratio of dilated intestinal length at late gestation and dilated stomach length (I/S ratio), and location of distal end of dilated bowel segment relative to spine were compared between CDO and high jejunal obstruction groups. The diagnostic performance of ultrasound indices was evaluated using receiver operating characteristics curve analysis. RESULTS: In 25 out of 26 CDO cases, the distal end of the dilated small intestine segment was located on the right side of spine, while that in the high jejunal obstruction group was located on the left side of spine. The dilated intestinal length and I/S ratio in CDO group were significantly smaller than those in high jejunal obstruction group (p < .05). Dilated intestinal length <51 mm or I/S ratio <1 showed high sensitivity (100, 100%) and specificity (96.1, 92.3%) for CDO (area under the curve: 0.995 and 0.988, respectively). There were no significant differences in the AUCs of dilated intestinal length and I/S ratio. Significant correlation of the site of obstruction in CDO with fetal dilated intestinal length and I/S ratio (r = 0.686; 0.660, p < .001, respectively) were noted. CONCLUSION: Location of the distal end of the dilated small intestine segment relative to the spine, dilated intestinal length, and I/S ratio may help differentiate fetal CDO from high jejunal obstruction. The latter two metrics were associated with the site of obstruction in CDO patients.

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.

Decline of stress resilience in aging rats: Focus on choroid plexus-cerebrospinal fluid-hippocampus.

OBJECTIVES: This study was designed to examine the mechanisms underlying decline of stress resilience in aged rats from the perspective of CP-CSF-hippocampus. METHODS: Male Wistar rats (7-8 weeks old or 20 months old) were subjected to chronic unpredictable mild stress (CUMS) for 6 weeks. The behavioral tests were conducted to assess anxiety, depression and cognitive function. Hippocampal neurogenesis, apoptosis and synaptic plasticity were detected by western blot (WB) and/or immunofluorescence (IF) assay. Differential expression of growth factors (GFs) and axon guidance proteins (AGPs) in CSF was analyzed using the quantitative proteomics approach. IF and WB were performed to detect expression of occludin-1, Ki-67/Transthyretin, and folate transporters in choroid plexus (CP). RESULTS: Decreased proliferation, impaired structure and transport function of CP were correlated with CSF composition alterations in stressed aging rats, including reduced 5-Methyltetrahydrofolate, growth factors and axon growth factors. Nutritional support of CSF upon hippocampus was attenuated, therefore affecting hippocampal plasticity. It has led to depression-like behaviors and cognitive deficits in stressful aged rats. CONCLUSIONS: Keeping normal structure and function of CP-CSF system may be a practical strategy for neuropsychological disorders in the elderly. This work provides evidential basis for CP transplant and CSF replacement therapy in future studies.

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.

Environmental enrichment mitigates PTSD-like behaviors in adult male rats exposed to early life stress by regulating histone acetylation in the hippocampus and amygdala.

Early life stress (ELS) can cause long-term changes in gene expression, affect cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood, in which the histone acetylation plays a crucial role. Studies have found that environmental enrichment (EE) mitigated the unfavorable outcomes of ELS. However, the underlying mechanism of the histone acetylation is not yet completely clear. The purpose of this study was to explore the effect of EE on the histone acetylation after ELS. In this study, using single prolonged stress (SPS) paradigm in early adolescent rats explored the long-term effects of ELS on behavior, the activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), as well as the acetylation levels of the lysine 9 site of histone H3 (H3K9) and lysine 12 site of histone H4 (H4K12) in the hippocampus and amygdala. Meanwhile, the protective effects of EE intervention were examined. We found that adult male rats exposed to ELS showed behavioral changes, including reduced locomotor activity, increased anxiety-like behaviors, impaired spatial learning and memory, enhanced contextual and cued fear memory, and the HATs/HDACs ratio and acetyl H3K9 (Ac-H3K9) and acetyl H4K12 (Ac-H4K12) were increased in the hippocampus and decreased in the amygdala. Furthermore, EE attenuated the behavioral abnormalities from ELS, possibly through down-regulating the activity of HATs in the hippocampus and up-regulating HDACs activities in the amygdala. These finding suggested that EE could ameliorate ELS-induced PTSD-like behaviors by regulating histone acetylation in the hippocampus and amygdala, reducing the susceptibility to PTSD in adulthood.

Luteolin Enhances Choroid Plexus 5-MTHF Brain Transport to Promote Hippocampal Neurogenesis in LOD Rats.

Folates, provided by food, are commonly used antidepressant synergists in late-onset depression (LOD). However, increased intake of folic acid in the elderly population might lead to the accumulation of unmetabolized folic acid in the systemic circulation, leading to enhanced deterioration of the central nervous system function. In addition, folates cannot access the brain directly because of the blood-brain barrier. Choroid plexus (CP) 5-methyltetrahydrofolate (5-MTHF) brain transport plays a critical role in regulating the cerebrospinal fluid (CSF) 5-MTHF content. Luteolin is a natural flavonoid that has antidepressant effects and is involved in the anti-folate resistance pathway. It remains unclear whether the antidepressant effects of luteolin are associated with the CP 5-MTHF brain transport. In this study, 20-21-month-old Wistar rats were exposed to the chronic unpredictable mild stress (CUMS) protocol for 6 consecutive weeks to explore the long-term effects of luteolin on behavior, 5-MTHF levels, hippocampal neurogenesis, and folate brain transport of the CP. In vitro primary hippocampal neural stem cells (NSCs) cultured in media containing 10% CSF from each group of rats and choroid plexus epithelial cells (CPECs) cultured in media containing 20 µM luteolin were treated with 100 µM corticosterone and 40 mg/ml D-galactose. We found that aged rats exposed to CUMS showed a significantly reduced sucrose preference, decreased locomotion activity in the open field test and accuracy of the Morris water maze test, increased immobility time in the forced swimming test, accelerated dysfunctional neurogenesis and neuronal loss in the dentate gyrus of LOD rats, as well as decreased CSF and hippocampus 5-MTHF levels, and zona occludens protein 1 (ZO-1), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC) protein levels. In vitro assays showed media containing 10% aged CSF or LOD+ Luteolin-CSF significantly increased the viability of CORT + D-gal-injured NSCs and alleviated dysfunctional neurogenesis and neuronal loss compared with the CORT + D-gal medium. However, media containing 10% LOD-CSF had no such effect. In the meantime, induction of CORT + D-gal significantly decreased the ZO-1, PCFT, RFC, and folate receptor alpha (FR-α) protein levels and transepithelial electrical resistance in rat CPECs. As expected, luteolin treatment was effective in improving these abnormal changes. These findings suggested that luteolin could ameliorate CUMS-induced LOD-like behaviors by enhancing the folate brain transport.

Gender differences in the associations between tobacco smoke exposure and depressive symptoms among U.S. adults: NHANES 2007-2018.

BACKGROUND: Findings concerning gender differences in the associations between tobacco smoke exposure (TSE) and depression are inconsistent. This study aimed to investigate the gender-specific associations between active and passive TSE with depressive symptoms in a large, nationally representative sample of U.S. adults. METHODS: Data were from 27,175 adults aged ≥20 years in the 2007-2018 National Health and Nutrition Examination Survey (NHANES). Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression was used to adjust for possible confounders. Whether the TSE-depression relationships may differ by age, race/ethnicity, socioeconomic status, body mass index (BMI), and self-reported health status was examined. RESULTS: After adjustment for lifestyle- and health-related variables, no significant associations between active (OR, 1.16 [95% CI, 0.87-1.55]) and passive TSE (OR, 0.84 [95% CI, 0.59-1.19]) and depressive symptoms were found among men. Among women, active TSE was associated with depressive symptoms (OR, 1.90 [95% CI, 1.51-2.39]), while the association for passive TSE was nonsignificant (OR, 1.11 [95% CI, 0.91-1.34]) after adjusting for lifestyle- and health-related variables. Interaction and subgroup analyses showed that self-reported health status could modify the relationship between passive TSE and depressive symptoms among women. Furthermore, a dose-response relationship between serum cotinine and depressive symptoms was found in women, but not in men. CONCLUSIONS: This study suggests a stronger TSE-depression association in women than in men. Understanding these gender-specific patterns and identifying the potential moderators of such relationships will enable better targeting of public health interventions.