Ligusticum chuanxiong Hort. Ameliorates Neuropathic Pain by Regulating Microglial M1 Polarization: A Study Based on Network Pharmacology.

Background: In traditional Chinese medicine, Ligusticum chuanxiong Hort. (LCH) is used to treat neuropathic pain (NP). This study was performed to investigate the underlying pharmacological mechanisms. Methods: The main components of the LCH were obtained from the TCMSP database. The targets of the active components were obtained using the Swiss Target Prediction database and HERB database. The NP-related genes were obtained from the CTD database and GeneCard database. Protein-protein interaction (PPI) network was constructed using the STRING platform and Cytoscape 3.9.0 software. GO and KEGG enrichment analyses were performed using the DAVID database. Interactions between the key components and hub target proteins were verified using molecular docking and molecular dynamics simulation. In addition, microglial cell line HMC3 was induced to polarize to the M1 phenotype using 100 ng/mL lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and enzyme-linked immunosorbent assays were used to detect the expression levels of M1 markers and inflammatory factors, respectively. Results: Seven LCH active components of LCH were identified, corresponding to 387 target genes. 2019 NP-related genes were obtained, and a total of 174 NP-related genes were identified as target genes that could be modulated by LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol were considered as the key components of LCH in the treatment of NP. SRC, BCL2, AKT1, HIF1A and HSP90AA1 were identified as the hub target proteins. GO analysis showed that 328 biological processes, 61 cell components, and 85 molecular functions were likely modulated by the components of LCH, and KEGG enrichment analysis showed that 132 signaling pathways were likely modulated by the components of LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol showed good binding activity with hub target proteins including SRC, BCL2, AKT1, and HSP90AA1. In addition, beta-sitosterol inhibited LPS-induced M1 polarization in HMC3 in vitro. Conclusion: This study provides a theoretical basis for the application of LCH in the treatment of NP through multicomponent, multitarget, and multiple pathways.

Characterization of the Mitogenome of the Genus Dendrocerus Ratzeburg (Hymenoptera: Megaspilidae) with the Specific Designed Primers.

In Hymenoptera, the monophyly of Evaniomorpha has been the focus of debate among different scholars. In this study, we sequenced two mitochondrial genomes of Dendrocerus (Hymenoptera: Megaspilidae) to analyze the mitochondrial genomic features of Dendrocerus and provide new molecular data for phylogenetic studies of Evaniomorpha. The mitogenome sizes of D. bellus and D. anisodontus were 15,445 bp and 15,373 bp, respectively, with the trnG of D. bellus missing. The nucleotide composition was significantly biased toward adenine and thymine, with A + T contents of 81.2% (D. bellus) and 82.4% (D. anisodontus). Using Ceraphron sp. (Ceraphronidae) as reference, the Ka/Ks values of NAD4L and NAD6 in D. anisodontus were both greater than one, indicating that non-synonymous mutations are favored by Darwinian selection, which is rare in other hymenopteran species. Compared with Ceraphon sp. gene order, nine operations were identified in D. anisodontus, including four reversals, four TDRLs (tandem duplication random losses) and one transposition, or four reversals and five TDRLs. Phylogenetic analysis of 40 mitochondrial genomes showed that Evaniomorpha was not a monophyletic group, which was also supported by the PBD values. Ceraphronoidea is a monophyletic group and is a sister to Aulacidae + Gasteruptiidae. Based on the conserved region of the newly sequenced mitochondrial genomes, a pair of specific primers MegaF/MegaR was designed for sequencing the COX1 genes in Megaspilidae and a 60% rate of success was achieved in the genus Dendrocerus.

Associations of maternal sleep trajectories during pregnancy and adverse perinatal outcomes: a prospective cohort study.

OBJECTIVE: Sleep problems are common in pregnant women and sleep is altered during pregnancy. However, the associations between sleep trajectory patterns and adverse maternal and neonatal outcomes are unclear. The current study aims to identify sleep trajectory patterns and explore their associations with adverse perinatal outcomes in a prospective cohort study. METHODS: Pregnant women (N = 232) completed the Pittsburgh Sleep Quality Index each trimester during pregnancy in Tianjin, China. Perinatal outcomes were extracted from the hospital delivery records. Latent class growth analysis (LCGA) described the trajectories of sleep timing, duration, and efficiency. Multivariable linear regression and multivariable logistic regression were employed to evaluate associations between sleep trajectory patterns and perinatal outcomes. RESULTS: Trajectories were identified for bedtime (early, 49.1%; delaying, 50.9%), wake-up time (early, 82.8% of the sample; late, 17.2%), duration (short, 5.2%; adequate 78.0%; excessive, 16.8%), and efficiency (high, 88.4%; decreasing, 11.6%). Compared with women in more optimal sleep groups, those in the late wake-up, excessive duration, and decreasing efficiency groups had babies with shorter birth lengths (ß range, -0.50 to -0.28, p < 0.05). Moreover, women in the decreasing efficiency group had babies with lower birth weight (ß, -0.44; p < 0.05). Women in the delaying bedtime group had greater odds of preterm delivery (OR, 4.57; p < 0.05), while those in the decreasing efficiency group had greater odds of cesarean section (OR, 3.12; p < 0.05). CONCLUSIONS: Less optimal sleep trajectory patterns during pregnancy are associated with perinatal outcomes. Therefore, early assessment of maternal sleep during pregnancy is significant for identifying at-risk women and initiating interventions to reduce perinatal outcomes.

G-4 inhibits triple negative breast cancer by inducing cell apoptosis and promoting LCN2-dependent ferroptosis.

Compound G-4 is a derivate of cyclin-dependent kinase inhibitor Rocovitine and showed strong sensitivity to triple negative breast cancer (TNBC) cells. In this study, the antitumor activity, mechanism and possible targets of G-4 in TNBC were investigated. Flow cytometry and immunoblotting showed that G-4 not only arrested the S phase of the cell cycle, but also induced apoptosis in TNBC cells via the mitochondrial pathway through inhibiting epidermal growth factor receptor (EGFR), AKT and MAPK pathways. In addition, G-4 induced the iron-mutagenesis process in TNBC cells and down-regulated differentially expressed gene lipid carrier protein 2 (LCN2) by RNA-seq. Moreover, G-4 elevated levels of cytosolic reactive oxygen species (ROS), lipid ROS, Fe and malondialdehyde (MDA), but decreased levels of superoxide dismutase (SOD) and glutathione (GSH), consistent with the effects of iron-mutagenic agonists Erastin and RSL3, which were inhibited by the iron inhibitor ferrostatin-1 (Fer-1). Furthermore, a LCN2 knockdown cell model was established by siRNA transfection, the IC50 of G-4 was increased nearly 100-fold, accompanied by a trend of no ferroptosis characteristic index. The results indicated that G-4 suppressed the malignant phenotype of TNBC, induced apoptosis by inhibiting EGFR pathway and promoted LCN2-dependent ferroptosis.

Exposure to phthalates and their alternatives in relation to biomarkers of inflammation and oxidative stress in adults: evidence from NHANES 2017-2018.

Phthalates and their alternatives are considered significant environmental risk factors that potentially influence inflammation and oxidative stress. However, their impact on biomarkers of inflammation and oxidative stress was inconsistent. This study aimed to explore the associations between phthalates and high-sensitivity C-reactive protein (hsCRP), gamma-glutamyl transferase (GGT), and white blood cell (WBC) counts, employing both univariate exposure and multivariate co-exposure models. For this analysis, a total of 1619 individuals aged 18 years and above, sourced from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018, were selected as subjects. We explored the associations between hsCRP, GGT, and WBC counts and eighteen different phthalate metabolites. Multiple linear regression analysis revealed significant associations between both MCNP and MEHP and hsCRP. We observed negative correlations of MCOP, MCPP, MHBP, and MONP with GGT. Conversely, MEHHP and MEHHTP exhibited positive correlations with GGT. Furthermore, MECPTP and MEHHTP showed positive correlations with WBC. Notably, we identified a non-linear relationship between phthalates and inflammation and oxidative stress markers. The Bayesian kernel machine regression (BKMR) analysis demonstrated a negative joint effect of the phthalates mixture on GGT, particularly at lower concentrations. The BKMR model also found that MEOHP and MHiBP were negatively associated with GGT. In contrast, MEHHP showed a significant positive association with GGT. Moderating effect analysis suggested that dietary inflammatory index (DII), income-to-poverty ratio (PIR), age, BMI, and physical activity influenced the association between phthalates and inflammation and oxidative stress. These findings contribute to a deeper understanding of the relationships between phthalates and inflammation and oxidative stress.

BMI-specific inflammatory response to phthalate exposure in early pregnancy: findings from the TMCHESC study.

Studies that have evaluated associations between phthalate metabolites and inflammation have reported inconsistent results among pregnant women, and it is unclear how body mass index (BMI) affects such relationships. Therefore, the present study aimed to examine the association between urinary phthalate metabolite concentrations and the levels of inflammatory biomarkers in the general circulation among 394 pregnant women selected from the Tianjin Maternal and Child Health Education and Service Cohort (TMCHESC) and to determine the role that BMI plays in the relationship. The concentrations of eight inflammatory biomarkers and three phthalate metabolites were measured in serum and urine samples, respectively. Multivariable linear modeling was conducted to examine the association between each phthalate and inflammatory biomarker while controlling for potential confounding factors in BMI-stratified subgroups. Restricted cubic splines were also utilised to explore potential non-linear relationships. In the high-BMI group, positive associations were observed between the levels of mono-n-butyl phthalate (MBP) and interleukin 1 beta (IL-1ß) (ß = 0.192; 95% CI: 0.033, 0.351), monoethyl phthalate (MEP), and C-reaction protein (CRP) (ß = 0.129; 95% CI 0.024, 0.233), and mono-ethylhexyl phthalate (MEHP) and interleukin 6 (IL-6) (ß = 0.146; 95% CI 0.016, 0.277). Restricted cubic spline models also revealed non-linear associations between the levels of MBP and interleukins 10 and 17A (IL-10 and IL-17A) and between MEP and interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) in pregnant women. These results suggest that phthalate exposure plays a potential role in promoting inflammation in the high-BMI group. While the precise mechanisms underlying the proinflammatory effects of phthalates are not fully understood, these findings suggest that BMI may play a role.

Metabolic Syndrome Is Associated with Poor Omicron Infection Prognosis While Inactivated Vaccine Improves the Outcome of Coronavirus Disease 2019 among Chinese Inhabitants: A Retrospective Observational Study from a Chinese Municipality.

Coronavirus disease 2019 (COVID-19) and metabolic syndrome (MetS) are currently highly prevalent diseases worldwide. Studies on clinical outcomes of patients with Omicron and MetS, especially after vaccination with an inactivated vaccine are limited. Herein, we explored the relationship between MetS and the outcome of Omicron infection. STUDY DESIGN: This was a retrospective observational study. METHODS: This study recruited 316 individuals with Omicron infection. The inpatient data from between 8 January and 7 February 2022 were obtained from designated isolation hospitals in Tianjin, China. Hierarchical and multivariable analysis was conducted on age, gender, number of complications, and vaccination status. RESULTS: Among the 316 study participants, 35.1% were diagnosed with MetS. The results showed that MetS was strongly associated with Intensive Unit Care (ICU) admission, Polymerase Chain Reaction (PCR) re-positivity, and severe COVID-19. The ICU admission rates of the unvaccinated individuals, those who received two-dose and full vaccination (3 doses), were 66.7%, 19.2%, and 0, respectively (p < 0.01). Two-dose and three-dose vaccinations significantly reduced PCR re-positivity. CONCLUSIONS: In summary, MetS increases the risk of ICU admission, PCR re-positivity, and severe COVID-19. MetS is a composite predictor of poor outcomes of Omicron infection. Two shots of inactivated vaccine, specifically three doses, effectively protect against Omicron even in the high-risk group.

Synthesis and mechanism of action of new purine derivatives against triple negative breast cancer.

Triple negative breast cancer (TNBC) is considered to be the most difficult subtype of breast cancer to treat because of its extremely prone to metastasis and the lack of targeted therapy drugs. New purine derivatives were synthesized and evaluated in a series of kinases and cell lines. The most active compounds 3g and 3j were selected based on their antiproliferative activities, then their pharmaceutical activity and mechanism in MDA-MB-231 cells were analyzed. The results in vitro indicated that compounds 3g and 3j can induce MDA-MB-231 cells apoptosis, and inhibit its migration and angiogenesis through influencing protein expression such as Bcl-2, Bax, Bcl-xl, P38, MMP2, MMP9, AKT and EGFR. In vivo results indicate that compounds 3g and 3j can inhibit tumor growth and metastasis and reduce the expression of Ki67 and CD31 protein in TNBC xenograft models. These findings not only broaden our understanding of the anti-TNBC effects and mechanisms of compounds 3g and 3j, but also provide new ideas and reference directions for the treatment of TNBC.

A J-shaped relationship between ketones and the risk of diabetic kidney disease in patients with type 2 diabetes: New insights from a cross-sectional study.

AIM: To investigate the association between circulating ß-hydroxybutyric acid (ßOHB) and diabetic kidney disease (DKD) risk in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 1388 patients with T2D were recruited. Participants were divided into high and normal ßOHB groups. Participants in the normal ßOHB group were divided into four subgroups according to ßOHB quartile (Q). The relationships of ßOHB with DKD and DKD subtype were analysed using chi-square and binary logistic regression. Restricted cubic splines were used to explore the non-linear correlation between ßOHB concentration and DKD risk in the total population. RESULTS: A higher prevalence of DKD was detected in the high compared with the normal ßOHB group (43.3% vs. 33.3%, P = .041). Participants in the Q4 group (ßOHB, 0.12-0.30 mM) had the lowest prevalence of DKD (P = .001). In the binary logistic regression model, the multivariable-adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for DKD risk were 2.30 (1.62-3.26) for Q1, 1.80 (1.23-2.62) for Q2 and 1.63 (1.10-2.41) for Q3 relative to Q4 (P < .001). Restricted cubic spline analyses suggested a J-shaped association of circulating ßOHB concentration with DKD risk. DKD risk was lowest at a serum ßOHB concentration of 0.183 mM (OR, 0.63; 95% CI, 0.52-0.77). CONCLUSIONS: A J-shaped relationship between circulating ketone level and DKD risk in patients with T2D was determined. Circulating ßOHB in the range of 0.12-0.30 mM was associated with a lower risk of DKD. Further studies are warranted to verify the causality and to elucidate the underlying mechanisms.

Effect of Circadian Distribution of Energy and Macronutrients on Gestational Weight Gain in Chinese Pregnant Women.

Gestational weight gain (GWG) may be affected by the timing of dietary intake. Previous studies have reported contradictory findings, possibly due to inconsistent characterizations of meal timing. We conducted a birth cohort study in Tianjin to determine the effect of daily energy and macronutrient distribution in mid and late pregnancy on GWG. Dietary intake information in the second and third trimesters used three 24-h dietary recalls, and meal timing was defined in relation to sleep/wake timing. The adequacy of GWG was assessed using recommendations from the Institute of Medicine guidelines. Pregnant women who had a relatively high average energy and macronutrient distribution in the late afternoon-early evening time window exhibited a greater GWG rate and a greater total GWG than that in morning time window during the third trimester (ß = 0.707; ß = 0.316). Carbohydrate intake in the morning of the second and third trimesters (ß = 0.005; ß = 0.008) was positively associated with GWG rates. Morning carbohydrate intake in the second trimester was also positively associated with total GWG (ß = 0.004). Fat intake in the morning of the third trimester (ß = 0.051; ß = 0.020) was positively associated with the GWG rates and total GWG. Excessive GWG of Chinese pregnant women was related closely to eating behavior focused on the late afternoon-early evening and carbohydrate and fat intake in the morning during the second and third trimesters.

Description of a new species of Conostigmus Dahlbom, 1858 (Hymenoptera: Megaspilidae) from China.

One new species of the genus Conostigmus Dahlbom, 1858, Conostigmus xui Cui and Wang sp. nov., from China is described. A key to the known species of Conostigmus from China is provided.

Associations between prenatal exposure to phthalates and birth weight: A meta-analysis study.

Previous studies have suggested that phthalates are associated with birth weight. However, most phthalate metabolites have not been fully explored. Therefore, we conducted this meta-analysis to assess the relationship between phthalate exposure and birth weight. We identified original studies that measured phthalate exposure and reported its association with infant birth weight in relevant databases. Regression coefficients (ß) with 95% confidence intervals (CIs) were extracted and analyzed for risk estimation. Fixed-effects (I2 ≤ 50%) or random-effects (I2 > 50%) models were adopted according to their heterogeneity. Overall summary estimates indicated negative associations of prenatal exposure to mono-n-butyl phthalate (pooled ß = -11.34 g; 95% CI: -20.98 to -1.70 g) and mono-methyl phthalate (pooled ß = -8.78 g; 95% CI: -16.30 to -1.27 g). No statistical association was found between the other less commonly used phthalate metabolites and birth weight. Subgroup analyses indicated that exposure to mono-n-butyl phthalate was associated with birth weight in females (ß = -10.74 g; 95% CI: -18.70 to -2.79 g). Our findings indicate that phthalate exposure might be a risk factor for low birth weight and that this relationship may be sex specific. More research is needed to promote preventive policies regarding the potential health hazards of phthalates.

Mucin Binding Protein of Lactobacillus casei Inhibits HT-29 Colorectal Cancer Cell Proliferation.

Many Lactobacillus casei strains are reported to exhibit anti-proliferative effects on colorectal cancer cells; however, the mechanism remains largely unknown. While there has been considerable interest in bacterial small metabolites such as short chain fatty acids, prior reports suggested that larger-sized molecules mediate the anti-proliferative effect of L. casei. Here, other possible ways of communication between gut bacteria and its host are investigated. LevH1 is a protein displayed on the surface of L. casei, and its mucin binding domain is highly conserved. Based on previous reports that the cell-free supernatant fractions decreased colorectal cell proliferation, we cloned the mucin binding domain of the LevH1 protein, expressed and purified this mucin binding protein (MucBP). It has a molecular weight of 10 kDa, is encoded by a 250 bp gene, and is composed primarily of a ß-strand, ß-turns, and random coils. The amino acid sequence is conserved while the 36th amino acid residue is arginine in L. casei CAUH35 and serine in L. casei IAM1045, LOCK919, 12A, and Zhang. MucBP36R exhibited dose-dependent anti-proliferative effects against HT-29 cells while a mutation of 36S abolished this activity. Predicted structures suggest that this mutation slightly altered the protein structure, thus possibly affecting subsequent communication with HT-29 cells. Our study identified a novel mode of communication between gut bacteria and their host.

Dendroceruslui (Hymenoptera, Ceraphronoidea, Megaspilidae): a new species of Dendroceruscarpenteri species-group from China.

Background: One new species of the genus Dendrocerus Ratzeburg, 1852, D.lui Li and Wang sp. nov. is described. A key to Chinese species of males is provided. The 28S sequence was generated to supplement the association of both sexes of the new species. New information: One new species of the genus Dendrocerus Ratzeburg, 1852, D.lui Li and Wang sp. nov. is described.

Tripartite motif protein 6 promotes hepatocellular carcinoma progression via multiple pathways.

Background/aim: Hepatocellular carcinoma (HCC) ranks among the most prevalent malignancies worldwide and the third leading cause of cancer-related death. The TRIM (tripartite motif-containing) protein family members had been reported to be involved in carcinogenesis and tumor progression. Here we aimed to explore the expression profile of TRIM6 in HCC and investigate its clinical significance as well as underlying mechanisms. Materials and methods: We retrospectively enrolled 138 HCC patients that underwent surgical resection in our hospital and tested protein expression level of TRIM6 through immunohistochemical staining. The correlation between TRIM6 and patients' characteristics was assessed by Chi-square test. Log-rank test and Cox hazard regression test were conducted for univariate and multivariate survival analyses, respectively. Two human HCC cell lines, Huh7 and Hep3B, were subjected for knockdown and overexpression assays, followed by phonotype tests including proliferation and invasion. Nude mice were used to generate xenograft model to validate our findings in vivo. Results: TRIM6 was highly expressed in HCC specimen compared to nontumorous liver tissues. Higher TRIM6 expression was correlated with larger tumor size, later tumor stage, and worse prognosis. According to the cellular experiments, TRIM6-knockdown resulted in decreased expression of cyclin B1, c-Myc, Snail, MMP2, and VEGF-A. Consistently, TRIM6-knockdown led to impaired HCC proliferation, invasion, and angiogenesis. In contrast, TRIM6 overexpression showed opposite effects. Finally, the oncogenic role of TRIM6 in HCC was validated by in vivo mice experiments. Conclusion: TRIM6 can serve as a novel prognostic factor for HCC, which functions by multiple signaling pathways.

Evaluating the effect of an artificial intelligence system on the anesthesia quality control during gastrointestinal endoscopy with sedation: a randomized controlled trial.

BACKGROUND: Sedative gastrointestinal endoscopy is extensively used worldwide. An appropriate degree of sedation leads to more acceptability and satisfaction. Artificial intelligence has rapidly developed in the field of digestive endoscopy in recent years and we have constructed a mature computer-aided diagnosis (CAD) system. This system can identify the remaining parts to be examined in real-time endoscopic procedures, which may help anesthetists use anesthetics properly to keep patients in an appropriate degree of sedation. AIMS: This study aimed to evaluate the effects of the CAD system on anesthesia quality control during gastrointestinal endoscopy. METHODS: We recruited 154 consecutive patients at Renmin Hospital of Wuhan University, including 76 patients in the CAD group and 78 in the control group. Anesthetists in the CAD group were able to see the CAD system's indications, while anesthetists in the control group could not. The primary outcomes included emergence time (from examination completion to spontaneous eye opening when doctors called the patients' names), recovery time (from examination completion to achievement of the primary recovery endpoints) and patient satisfaction scores. The secondary outcomes included anesthesia induction time (from sedative administration to successful sedation), procedure time (from scope insertion to scope withdrawal), total dose of propofol, vital signs, etc. This trial was registered in the Primary Registries of the WHO Registry Network, with registration number ChiCTR2100042621. RESULTS: Emergence time in the CAD group was significantly shorter than that in the control group (p < 0.01). The recovery time was also significantly shorter in the CAD group (p < 0.01). Patients in the CAD group were significantly more satisfied with their sedation than those in control group (p < 0.01). Vital signs were stable during the examinations in both groups. Propofol doses during the examinations were comparable between the two groups. CONCLUSION: This CAD system possesses great potential for anesthesia quality control. It can improve patient satisfaction during endoscopic examinations with sedation. TRIAL REGISTRATION: ChiCTR2100042621.

Complete genomic sequences and comparative analysis of two Orf virus isolates from Guizhou Province and Jilin Province, China.

Orf virus (ORFV, species Orf virus) belongs to the typical species of the Parapoxvirus genus of the family Poxviridae, which infects sheep, goats, and humans with worldwide distribution. Although outbreaks of Orf have been reported sequentially in several Chinese provinces, the epidemiology of Orf and genetic diversity of ORFV strains still needs to be further characterized. To further reveal the genomic organization of the ORFV-GZ18 and ORFV-CL18 isolates, the complete genome sequences of two recently obtained ORFV isolates were sequenced using the next-generation sequencing technology and analyzed, which had been deposited in the GenBank database under accession number MN648218 and MN648219, respectively. The complete genomic sequence of ORFV-CL18 was 138,495 bp in length, including 131 potential open reading frames (ORFs) flanked by inverted terminal repeats (ITRs) of 3481 bp at both ends, which has genomic structure typical Parapoxviruses. The overall genomic organization of the fully sequenced genome of ORFV-GZ18 was consistent with ORFV-CL18 genome, with a complete genome size of 138,446 nucleotides, containing 131 ORFs flanked by ITRs of 3469 bp. Additionally, the overall G + C contents of ORFV-GZ18 and ORFV-CL18 genome sequences were about 63.9% and 63.8%, respectively. The phylogenetic analysis showed that both ORFV-GZ18 and ORFV-CL18 were genetically closely related to ORFV-SY17 derived from sheep. In summary, the complete genomic sequences of ORFV-GZ18 and ORFV-CL18 are reported, with the hope it will be useful to investigate the host range, geographic distribution, and genetic evolution of the virus in Southern West and Northern East China.

Regulation of Th17/Treg Balance by 27-Hydroxycholesterol and 24S-Hydroxycholesterol Correlates with Learning and Memory Ability in Mice.

Dysregulation of cholesterol metabolism and its oxidative products-oxysterols-in the brain is known to be associated with neurodegenerative diseases. It is well-known that 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) are the main oxysterols contributing to the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanism of how 27-OHC and 24S-OHC cause cognitive decline remains unclear. To verify whether 27-OHC and 24S-OHC affect learning and memory by regulating immune responses, C57BL/6J mice were subcutaneously injected with saline, 27-OHC, 24S-OHC, 27-OHC+24S-OHC for 21 days. The oxysterols level and expression level of related metabolic enzymes, as well as the immunomodulatory factors were measured. Our results indicated that 27-OHC-treated mice showed worse learning and memory ability and higher immune responses, but lower expression level of interleukin-10 (IL-10) and interferon (IFN-λ2) compared with saline-treated mice, while 24S-OHC mice performed better in the Morris water maze test than control mice. No obvious morphological lesion was observed in these 24S-OHC-treated mice. Moreover, the expression level of interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 3α (MIP-3α) were significantly decreased after 24S-OHC treatment. Notably, compared with 27-OHC group, mice treated with 27-OHC+24S-OHC showed higher brain 24S-OHC level, accompanied by increased CYP46A1 expression level while decreased CYP7B1, retinoic acid-related orphan receptor gamma t (RORγt) and IL-17A expression level. In conclusion, our study indicated that 27-OHC is involved in regulating the expression of RORγt, disturbing Th17/Treg balance-related immune responses which may be associated with the learning and memory impairment in mice. In contrast, 24S-OHC is neuroprotective and attenuates the neurotoxicity of 27-OHC.

Social Support and Self-Efficacy as Mediating Factors Affecting the Association Between Depression and Medication Adherence in Older Patients with Coronary Heart Disease: A Multiple Mediator Model with a Cross-Sectional Study.

PURPOSE: Medication non-adherence is a major public health issue. Recent evidence suggests that depression, inadequate social support, and lower levels of self-efficacy are associated with poor medication adherence. However, the mechanism underlying the association among depression, social support, self-efficacy and medication adherence is unclear. This study aims to examine the mediating role of social support and self-efficacy between depression and medication adherence in older patients with coronary heart disease. PATIENTS AND METHODS: Data were collected from 238 hospitalized older patients with coronary heart disease. Depression, social support, self-efficacy, and medication adherence were assessed using structured questionnaires. A serial multiple mediation model was tested using the PROCESS macro for SPSS. RESULTS: A total of 238 older patients with CHD with a mean age of 70.5 years were involved in this cross-sectional study. Depression was negatively correlated with medication adherence in older patients with coronary heart disease. Social support and self-efficacy were positively associated with medication adherence, and fully mediated the relationship between depression and medication adherence. Three mediation paths were included in the model: (a) social support, (b) chain combination of social support and self-efficacy, and (c) self-efficacy. CONCLUSION: Social support and self-efficacy explain the association of depression and medication adherence in older CHD patients and may be the keys target for enhanced intervention to improve medication adherence in older CHD patients with depression.