Evaluation of the in vitro and in vivo antimicrobial activity of alkaloids prepared from Chelidonium majus L. using MRSA- infected C. elegans as a model host.

Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.

Short-term exposures to PM2.5, PM2.5 chemical components, and antenatal depression: Exploring the mediating roles of gut microbiota and fecal short-chain fatty acids.

BACKGROUND: PM2.5 and its chemical components increase health risks and are associated with depression and gut microbiota. However, there is still limited evidence on whether gut microbiota and short-chain fatty acids (SCFAs) mediate the association between PM2.5, PM2.5 chemical components, and antenatal depression. The purpose of this study was to investigate the mediating role of maternal gut microbiota in correlations between short-term exposure to PM2.5, short-term exposure to PM2.5 chemical components, and antenatal depression. METHODS: Demographic information and stool samples were collected from 75 pregnant women in their third trimester. Their exposure to PM2.5 and PM2.5 chemical components was measured. Participants were divided into the non-antenatal depression group or the antenatal depression group according to the cut-off of 10 points on the Edinburgh Postnatal Depression Scale (EPDS). The gut microbiota were analyzed using the 16 S rRNA-V3/V4 gene sequence, and the concentration of PM2.5 and its chemical components was calculated using the Tracking Air Pollution in China (TAP) database. Gas chromatography-mass spectrometry was used to analyze SCFAs in stool samples. In order to assess the mediating effects of gut microbiota and SCFAs, mediation models were utilized. RESULTS: There were significant differences between gut microbial composition and SCFAs concentrations between the non-antenatal depression group and the antenatal depression group. PM2.5 and its chemical components were positively associated with EPDS scores and negatively associated with genera Enterococcus and Enterobacter. Genera Candidatus_Soleaferrea (ß = -7.21, 95%CI -11.00 to -3.43, q = 0.01) and Enterococcus (ß = -2.37, 95%CI -3.87 to -0.87, q = 0.02) were negatively associated with EPDS scores, indicating their potential protective effects against antenatal depression. There was no significant association between SCFAs and EPDS scores. The mediating role of Enterococcus between different lagged periods of PM2.5, PM2.5 chemical component exposure, and antenatal depression was revealed. For instance, Enterococcus explained 29.23% (95%CI 2.16-87.13%, p = 0.04) of associations between PM2.5 exposure level at the day of sampling (lag 0) and EPDS scores. CONCLUSION: Our study highlights that Enterococcus may mediate the associations between PM2.5, PM2.5 chemical components, and antenatal depression. The mediating mechanism through which the gut microbiota influences PM2.5-induced depression in pregnant women still needs to be further studied.

Construction of a prognostic model based on genome-wide methylation analysis of miRNAs for hepatocellular carcinoma.

Aim: Using the methylation level of miRNA genes to develop a prognostic model for patients with hepatocellular carcinoma (HCC). Materials & methods: least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed to develop a prognostic model. One miRNA in the model was selected for verification. Results: A prognostic model was developed using eight miRNAs. The areas under the curve for predicting overall survival at 1, 3 and 5 years were 0.75, 0.81 and 0.81. miR-223 was found to be hypomethylated in 160 HCC tissues, and its methylation level was associated with Barcelona Clinic Liver Cancer stages and the prognosis of patients with HCC. Conclusion: The prognostic model based on miRNA methylation levels has the capability to partially forecast the prognosis of patients with HCC.

Ezrin's role in gastric cancer progression: Implications for immune microenvironment modulation and therapeutic potential.

At present, surgical resection is the most effective method for the treatment of gastric cancer. However, death caused by inoperable metastasis is still very common, despite research in this area. The mechanisms underlying the occurrence, development, and metastasis of gastric cancer are not fully understood. Ezrin, a plasma membrane-microfilament junction participates in a variety of cellular activities and is closely related to tumorigenesis and development. Few studies have explored the relationship between the tumor immune microenvironment and ezrin expression in gastric cancer. In this study, we used proteomic techniques to analyze the differentially expressed proteins between the gastric cancer cell lines MKN-45 and HGC-27 and screened ezrin as the target protein. We collected patient information from The TCGA and GEO databases, and the results showed that ezrin was positively correlated with adverse clinical features. We further explored the relationship between ezrin expression levels, immune microenvironment, and genomic changes. We found that ezrin was involved in immune regulation and genomic instability in gastric cancer. When the expression of ezrin is high, immune cell infiltration also increases. We also predicted that ezrin is closely related to immunotherapy and chemosensitivity. Single-cell transcriptome data showed that the ezrin gene was mainly expressed in B cells and epithelial cells, and the expression of EZR in these epithelial cells was positively correlated with the epithelial-mesenchymal transformation pathway and Pi3k-AKT pathway score. Through functional verification of the stably transfected cell line constructed by lentivirus, the results of the liver metastasis model in nude mice suggested that high expression of ezrin leads to the formation of more metastatic foci. In summary, our results clarify the prognostic, immunological, and therapeutic value of ezrin in gastric cancer and provide a theoretical basis for more accurate treatment.

Phocaeicola vulgatus alleviates diet-induced metabolic dysfunction-associated steatotic liver disease progression by downregulating histone acetylation level via 3-HPAA.

Diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

Perinatal depression and infant and toddler neurodevelopment: A systematic review and meta-analysis.

Many studies have focused on the effect of perinatal depression on neurodevelopment among children and adolescents. However, only a few studies have explored this relationship in infants and toddlers with inconsistent results. We performed a systematic review and meta-analysis to evaluate the association between perinatal depression and infant and toddler neurodevelopment during the first two postnatal years. Twenty-three studies were included in this meta-analysis. Perinatal depression was associated with poorer cognitive (Cohen's d = -0.19, SE= 0.06, 95% CI = -0.30 to -0.08), language (Cohen's d = -0.24, SE = 0.09, 95% CI = -0.40 to -0.07), and motor (Cohen's d = -0.15, SE = 0.05, 95% CI = -0.26 to -0.05) development. Subgroup analyses showed that the types of maternal depression (prenatal depression vs. postnatal depression), the method of measuring maternal depression (rating scale vs. diagnostic interview), and the time interval between assessment of exposure and outcome had an impact on the observed effect about neurodevelopment of infants and toddlers. In addition, the results of our study pointed to a stronger significant association between prenatal depression and cognitive, language, and motor delays in infants and toddlers, whereas the association between postnatal depression and cognitive, language, and motor delays in infants and toddlers was not statistically significant. In conclusion, this study provided convincing evidence that the perinatal window is a sensitive period for offspring neurodevelopment.

Alterations of the gut microbiota and fecal short-chain fatty acids in women undergoing assisted reproduction.

CONTEXT: The community structure of gut microbiota changes during pregnancy, which also affects the synthesis of short-chain fatty acids (SCFAs). However, the distribution of gut microbiota composition and metabolite SCFA levels are poorly understood in women undergoing assisted reproductive technology (ART). AIMS: To evaluate the changes in gut microbiota composition and metabolic SCFAs in women who received assisted reproduction treatment. METHODS: Sixty-three pregnant women with spontaneous pregnancy (SP) and nine with ART pregnancy were recruited to provide fecal samples. Gut microbiota abundance and SCFA levels were determined by 16S ribosomal RNA (rRNA) gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS). KEY RESULTS: The ART group showed decreased alpha diversity (the species richness or evenness in a sample). The principal coordinates analysis (a method of analysing beta diversity) showed significant difference in gut microbiota between the ART group versus the SP group (unweighted UniFrac distance, R 2 =0.04, P =0.003). Proteobacteria , Blautia and Escherichia-Shigella were enriched in the ART group, whereas the relative abundance of beneficial intestinal bacteria Faecalibacterium was lower than in the SP group. Different modes of conception were associated with several SCFAs (valeric acid (r =-0.280; P =0.017); isocaproic acid (r =-0.330; P =0.005); caproic acid (r =-0.336; P =0.004)). Significantly different SCFAs between the two groups were synchronously associated with the differential gut microbiota. CONCLUSIONS: The diversity and abundance of gut microbiota and the levels of SCFAs in women undergoing ART decreased. IMPLICATIONS: The application of ART shaped the microbial composition and metabolism, which may provide critical information for understanding the biological changes that occur in women with assisted reproduction.

Rosavin extends lifespan via the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Rosavin, a phenylpropanoid glycoside, is the specific index component and one of the main active components of Rhodiola rosea. Currently, there are few studies describing the antiaging effect of rosavin, and most of them are mainly based on in vitro antioxidant research. Our study aimed to investigate the antiaging activities and mechanisms of rosavin in Caenorhabditis elegans. Using Caenorhabditis elegans as the model, the lifespan of Caenorhabditis elegans under various stressors (heat and juglone) and normal conditions was studied, and the antioxidant activities of rosavin were discussed. To discover the underlying mechanisms, we analyzed daf-16 nuclear localization, the expression of the sod-3p::GFP fusion protein, mRNA levels, and loss-of-function mutants of IIS-associated genes. The results showed that rosavin significantly improved the lifespan of Caenorhabditis elegans under stress and normal conditions. Rosavin can increase the expression and activity of antioxidant enzymes and suppress the generation of malondialdehyde and ROS in nematodes. Additionally, it promotes the nuclear localization of daf-16 and improves the expression of the sod-3 gene in Caenorhabditis elegans. The data revealed that rosavin activated the insulin/IGF-1 signaling pathway by downregulating the upstream components daf-2 and age-1. In summary, these results verify that rosavin could increase the lifespan of Caenorhabditis elegans through the insulin/IGF-1 signaling pathway.

Combined impact of Hepatitis B virus and gestational diabetes mellitus on ultrasound-measured fetal growth and adverse perinatal outcomes: A seven-year retrospective study.

AIMS: To investigate the impact of pregnancy with combined hepatitis B virus (HBV) infection and Gestational diabetes mellitus (GDM) on fetal growth and adverse perinatal outcomes. METHODS: All the pregnant women with HBV infection and/or GDM who delivered at Women's Hospital, Zhejiang University between January 2015, and September 2022 were included. A total of 1633 pregnant women were recruited in the final analysis, including 409 women with HBV infection and GDM, 396 with HBV infection only, 430 with GDM only, and 398 without HBV infection and GDM. Linear and logistic regression models were used to study the impact of pregnancy with combined HBV infection and GDM on fetal growth and adverse perinatal outcomes. RESULTS: Pregnancy with combined HBV infection and GDM was associated with increased Z-scores on primary fetal ultrasound parameters and significantly increased the risk of fetal femur length overgrowth (OR: 2.88, 95 % CI: 1.13 âˆ¼ 7.35), placental abruption (OR: 3.64, 95 % CI: 1.18 âˆ¼ 11.22), and macrosomia (OR: 4.19, 95 % CI: 1.66 âˆ¼ 10.56) compared to pregnancy without HBV infection and GDM. CONCLUSIONS: Both maternal HBV infection and GDM are independently associated with adverse perinatal outcomes. Their combination further increases the risk of adverse perinatal outcomes.

Predictors of body image dissatisfaction among women at different stages of pregnancy:A cross-sectional study.

OBJECTIVE: To explore the levels and predictors of body image dissatisfaction among women at different stages of pregnancy. DESIGN: This was a cross-sectional study design. SETTING AND PARTICIPANTS: A total of 863 Chinese pregnant women were recruited from a tertiary hospital via a convenience sampling method. MEASUREMENT AND FINDINGS: Eligible participants completed a demographic questionnaire and self-reported measures of body image dissatisfaction, pregnancy-related anxiety, prenatal depression, and appearance comparison. Results showed no statistical difference in body image dissatisfaction levels among early-mid pregnancy (47.6 ± 6.17), late-mid pregnancy (47.3 ± 7.56), and late pregnancy stages (48.4 ± 6.22). The generalized linear model showed that gestational weight gain, pregnancy-related anxiety, own/family's perception of pregnancy weight, and current ideal weight change were predictors of body image dissatisfaction in the early-mid pregnancy stage. In addition, pre-pregnancy BMI, appearance comparison, own /family's perception of pregnancy weight, current ideal weight change, and overeating during pregnancy significantly predicted body image dissatisfaction in the late-mid pregnancy stage. Predictors of body image dissatisfaction in the late pregnancy stage comprised planned pregnancy, pre-pregnancy eating disorders, own perception of pregnancy weight, current ideal weight change, pregnancy-related anxiety, and prenatal depression. KEY CONCLUSION AND IMPLICATION FOR PRACTICE: The findings suggest that predictors of body image dissatisfaction differed according to pregnancy stage. Self-perception of pregnancy weight was primary predictor of body image dissatisfaction. Healthcare professionals are recommended to provide prenatal health education to reduce own/family's negative perception of pregnancy weight, so as to alleviate the body image dissatisfaction level of pregnant women.

Association between gut microbiota and its functional metabolites with prenatal depression in women.

Background: The gut microbiota may affect mood through the microbiota-gut-brain axis. The purpose of this study was to examine the effect of the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), on prenatal depression and to determine the role of 5-hydroxytryptamine (5-HT) on prenatal depression in association with the gut microbiota and its metabolites (i.e. SCFAs). Methods: Eighty-six pregnant women in the third trimester were recruited. Prenatal depression was determined by a score of 10 via the Edinburgh Postpartum Depression Scale. Demographic data, stool, and blood samples were collected. The gut microbiota and its metabolites SCFAs were determined by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry analysis. Plasma 5-HT was determined by gas chromatography-mass spectrometry analysis. Results: After controlling relevant covariates, our results found the higher the abundance of Candidatus_Soleaferrea, the lower the risk of prenatal depression; the higher the concentration of propanoic acid, the higher risk of prenatal depression. Our results also found the lower the plasma 5-HT, the higher the risk of prenatal depression, and 5-HT was related to unclassified_c_Clostridia and NK4A214_group. However, results of this study did not support the moderating effect of plasma 5-HT on the association of Candidatus_Soleaferrea or propionic acid with prenatal depression. Conclusions: Results of this study supported that changes in certain gut microbiota, SCFAs, and plasma 5-HT during pregnancy were associated with prenatal depression. This finding provides new ideas for interventions based on diet or probiotics to regulate mood during pregnancy.

Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases.

Inflammation is a natural host defense mechanism that protects the body from pathogenic microorganisms. A growing body of research suggests that inflammation is a key factor in triggering other diseases (lung injury, rheumatoid arthritis, etc.). However, there is no consensus on the complex mechanism of inflammatory response, which may include enzyme activation, mediator release, and tissue repair. In recent years, p38 MAPK, a member of the MAPKs family, has attracted much attention as a central target for the treatment of inflammatory diseases. However, many p38 MAPK inhibitors attempting to obtain marketing approval have failed at the clinical trial stage due to selectivity and/or toxicity issues. In this paper, we discuss the mechanism of p38 MAPK in regulating inflammatory response and its key role in major inflammatory diseases and summarize the synthetic or natural products targeting p38 MAPK to improve the inflammatory response in the last five years, which will provide ideas for the development of novel clinical anti-inflammatory drugs based on p38 MAPK inhibitors.

Engineered NIR-II fluorophores with ultralong-distance molecular packing for high-contrast deep lesion identification.

The limited signal of long-wavelength near-infrared-II (NIR-II, 900-1880 nm) fluorophores and the strong background caused by the diffused photons make high-contrast fluorescence imaging in vivo with deep tissue disturbed still challenging. Here, we develop NIR-II fluorescent small molecules with aggregation-induced emission properties, high brightness, and maximal emission beyond 1200 nm by enhancing electron-donating ability and reducing the donor-acceptor (D-A) distance, to complement the scarce bright long-wavelength emissive organic dyes. The convincing single-crystal evidence of D-A-D molecular structure reveals the strong inhibition of the π-π stacking with ultralong molecular packing distance exceeding 8 Å. The delicately-designed nanofluorophores with bright fluorescent signals extending to 1900 nm match the background-suppressed imaging window, enabling the signal-to-background ratio of the tissue image to reach over 100 with the tissue thickness of ~4-6 mm. In addition, the intraluminal lesions with strong negatively stained can be identified with almost zero background. This method can provide new avenues for future long-wavelength NIR-II molecular design and biomedical imaging of deep and highly scattering tissues.

Effects of psychosocial sleep interventions on improving infant sleep and maternal sleep and mood: A systematic review and meta-analysis.

Infant sleep problems are prevalent and have a negative impact on infant growth and development, maternal sleep, and maternal mood. The effects of psychosocial sleep interventions on infant sleep and maternal sleep and mood are unclear. This study aimed to systematically evaluate the effects of psychosocial sleep interventions on improving infant sleep, including nocturnal total sleep time, daytime total sleep, total sleep time, night wakings, and maternal sleep and mood problems (ie, depression and fatigue). We searched PubMed, Web of Science, Cochrane Library, Embase, EBSCO, OpenGrey, DeepBlue, China National Knowledge Infrastructure, and Wanfang databases. We focused on randomized controlled trials examining the effectiveness of psychosocial sleep interventions on infant sleep. The study was preregistered at the International Prospective Register of Systematic Reviews (CRD42022301654). Thirteen studies from 5889 articles were included in the review, which found that psychosocial sleep interventions improved infant nocturnal total sleep time (0.28 [0.04-0.52], p < 0.05, I2 = 83.9%) and maternal depression (-0.10 [-0.28 to -0.08], p < 0.05, I2 = 8.7%). To test and explore heterogeneity, we used the I2 statistic, influence analysis, subgroup analyses, and subgroup meta-analyses. Funnel plots and Egger's tests revealed no evidence of publication bias. Psychosocial sleep interventions improved infant nocturnal total sleep time and maternal depression. Future research should include more randomized controlled trials examining the effect of psychosocial sleep interventions on the improvement of maternal sleep and fatigue.

Cumulative and lagged effects of varying-sized particulate matter exposure associates with toddlers' gut microbiota.

Particulate matter (PM) is an important component of air pollutants and is associated with various health risks. However, the impact of PM on toddlers' gut microbiota is rarely investigated. This study aimed to assess the cumulative and lagged effects of varying-sized PMs on toddlers' gut microbiota. We collected demographic information, stool samples, and exposure to PM from 36 toddlers aged 2-3 years. The toddlers were divided into warm season group and cooler season group according to the collection time of stool samples. The gut microbiota was processed and analyzed using 16S rRNA V3-V4 gene regions. The concentration of PM was calculated using China High Air Pollutants (CHAP) database. To assess the mixed effects of varying-sized PM, multiple-PM models were utilized. There were significant differences between the community composition, α- and ß-diversity between two groups. In multiple-PM models, there was a significant effect of weight quantile sum (PM1, PM2.5, and PM10) on α-diversity indices. In weight quantile sum models, after adjusting for a priori confounders, we found a negative effect of weight quantile sum on Enterococcus (ß = -0.134, 95% CI -0.263 to -0.006), positive effects of weight quantile sum on unclassified_f__Ruminococcaceae (ß = 0.247, 95% CI 0.102 to 0.393), Ruminococcus_1 (ß = 0.444, 95% CI 0.238 to 0.650), unclassified_f__Lachnospiraceae (ß = 0.278, 95% CI 0.099 to 0.458), and Family_XIII_AD_3011_group (ß = 0.254, 95% CI 0.086 to 0.422) in WSG and CSG. In lagged weight quantile sum models, the correlation between lag time PM levels and the gut microbiota showed seasonal trends, and weights of PM changed with lag periods. This is the first study to highlight that cumulative and lagged effects of PMs synergistically affect the diversities (α- and ß-diversity) and abundance of the gut microbiota in toddlers. Further research is needed to explore the mediating mechanism of varying-sized PMs exposure on the gut microbiota in toddlers.

Global development of artificial intelligence in cancer field: a bibliometric analysis range from 1983 to 2022.

Background: Artificial intelligence (AI) is widely applied in cancer field nowadays. The aim of this study is to explore the hotspots and trends of AI in cancer research. Methods: The retrieval term includes four topic words ("tumor," "cancer," "carcinoma," and "artificial intelligence"), which were searched in the database of Web of Science from January 1983 to December 2022. Then, we documented and processed all data, including the country, continent, Journal Impact Factor, and so on using the bibliometric software. Results: A total of 6,920 papers were collected and analyzed. We presented the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions, and research focus and hotspots in AI-based cancer research. Conclusion: This study systematically summarizes the current research overview of AI in cancer research so as to lay the foundation for future research.

Inflammatory cytokines and prenatal depression: Is there a mediating role of maternal gut microbiota?

OBJECTIVE: The mechanism of levels of inflammatory cytokines that affects brain function and mood through gut microbiota has not been fully elucidated. This study aimed to investigate the potential mediating role of gut microbiota between maternal inflammatory cytokines levels and prenatal depression. DESIGN: There were 29 women in the prenatal depression group and 27 women in the control group enrolled in this study. The Edinburgh Postnatal Depression Scale (EPDS) score of 10 was considered the cut-off value for prenatal depression. We collected demographic information, stool and blood samples. The gut microbiota was profiled using V3-V4 gene sequence of 16S rRNA, and the concentration of inflammatory cytokines were analyzed. The mediation model was analyzed by using the model 4 in the process procedure for SPSS. RESULTS: There were significance differences in the concentration of interleukin-1beta (IL-1ß)(Z = -2.383, P = 0.017) and IL-17A (Z = -2.439, P = 0.015) between the prenatal depression group and control group. There was no significant difference in α- diversity and ß-diversity between the two groups. Intestinibacter (OR: 0.012; 95% CI, 0.001-0.195) and Escherichia_Shigella (OR: 0.103; 95% CI, 0.014-0.763) were protective factors for prenatal depression, while Tyzzerella (OR: 17.941; 95% CI, 1.764-182.445) and Unclassified_f_Ruminococcaceae (OR: 22.607; 95% CI, 1.242-411.389) were risk factors. And Intestinibacter play a mediation effect between IL-17A and prenatal depression. CONCLUSION: Maternal gut microbiota is a significant mediator of the relationship between inflammatory cytokines and prenatal depression. Further research is still needed in exploring the mediating mechanisms of gut microbiota between inflammatory cytokines and depression.

Synthesis, anti-aging and mechanism of magnolol derivatives.

Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components of Houpoea officinalis for antioxidation and anti-aging. To enhance the antioxidant activity of magnolol, the different sites of magnolol were structurally modified in this experiment, and a total of 12 magnolol derivatives were obtained. Based on the preliminary exploration of the anti-aging effect of magnolol derivatives in a Caenorhabditis elegans (C. elegans) model. Our results indicate that the active groups of magnolol exerting anti-aging effects were allyl groups and hydroxyl on the phenyl. Meanwhile, the anti-aging effect of the novel magnolol derivative M27 was found to be significantly superior to that of magnolol. To investigate the effect of M27 on senescence and the potential mechanism of action, we investigated the effect of M27 on senescence in C. elegans. In this study, we investigated the effect of M27 on C. elegans physiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance in C. elegans was explored by acute stress experiments. The mechanism of M27 anti-aging was investigated by measuring ROS content, DAF-16 nuclear translocation, sod-3 expression, and lifespan of transgenic nematodes. Our results indicate that M27 prolonged the lifespan of C. elegans. Meanwhile, M27 improved the healthy lifespan of C. elegans by improving pharyngeal pumping ability and reducing lipofuscin accumulation in C. elegans. M27 increased resistance to high temperature and oxidative stress in C. elegans by reducing ROS. M27 induced DAF-16 translocation from cytoplasm to nucleus in transgenic TJ356 nematodes and upregulated the expression of sod-3 (a gene downstream of DAF-16) in CF1553 nematodes. Furthermore, M27 did not extend the lifespan of daf-16, age-1, daf-2, and hsp-16.2 mutants. This work suggests that M27 may ameliorate aging and extend lifespan in C. elegans through the IIS pathway.

TRPM2 Mediates Hepatic Ischemia-Reperfusion Injury via Ca2+-Induced Mitochondrial Lipid Peroxidation through Increasing ALOX12 Expression.

Hepatic ischemia-reperfusion (IR) injury is a serious clinical problem that complicates liver resection and transplantation. Despite recent advances in understanding of the pathophysiology of hepatic IR injury, effective interventions and therapeutics are still lacking. Here, we examined the role of transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable, non-selective cation channel, in mediating hepatic IR injury. Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction, inflammation, and cell death in mice. Moreover, RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways. Consistently, as a ferroptosis inducer, (1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this. Interestingly, TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca2+-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase (ALOX12), which results in mitochondrial lipid peroxidation during hepatic IR injury. Furthermore, hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion, both in vitro and in vivo. Collectively, these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca2+-induced ALOX12 expression, indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases, such as during liver resection and transplantation.

Does PM1 exposure during pregnancy impact the gut microbiota of mothers and neonates?

BACKGROUND: Ambient air pollutant exposure can change the composition of gut microbiota at 6-months of age, but there is no epidemiological evidence on the impacts of exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during pregnancy on gut microbiota in mothers and neonates. We aimed to determine if gestational PM1 exposure is associated with the gut microbiota of mothers and neonates. METHODS: Leveraging a mother-infant cohort from the central region of China, we estimated the exposure concentrations of PM1 during pregnancy based on residential address records. The gut microbiota of mothers and neonates was analyzed using 16 S rRNA V3-V4 gene sequences. Functional pathway analyses of 16 S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The impact of PM1 exposure on α-diversity, composition, and function of gut microbiota in mothers and neonates was evaluated using multiple linear regression, controlling for nitrogen dioxide (NO2) and ozone (O3). Permutation multivariate analysis of variance (PERMANOVA) was used to analyze the interpretation degree of PM1 on the sample differences at the OTU level using the Bray-Curtis distance algorithm. RESULTS: Gestational PM1 exposure was positively associated with the α-diversity of gut microbiota in neonates and explained 14.8% (adj. P = 0.026) of the differences in community composition among neonatal samples. In contrast, gestational PM1 exposure had no impact on the α- and ß-diversity of gut microbiota in mothers. Gestational PM1 exposure was positively associated with phylum Actinobacteria of gut microbiota in mothers, and genera Clostridium_sensu_stricto_1, Streptococcus, Faecalibacterium of gut microbiota in neonates. At Kyoto Encyclopedia of Genes and Genomes pathway level 3, the functional analysis results showed that gestational PM1 exposure significantly down-regulated Nitrogen metabolism in mothers, as well as Two-component system and Pyruvate metabolism in neonates. While Purine metabolism, Aminoacyl-tRNA biosynthesis, Pyrimidine metabolism, and Ribosome in neonates were significantly up-regulated. CONCLUSIONS: Our study provides the first evidence that exposure to PM1 has a significant impact on the gut microbiota of mothers and neonates, especially on the diversity, composition, and function of neonatal meconium microbiota, which may have important significance for maternal health management in the future.