Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation.

The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.

Bifidobacterium adolescentis-derived hypaphorine alleviates acetaminophen hepatotoxicity by promoting hepatic Cry1 expression.

Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

Qi-dan-dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway.

CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND METHODS: The compounds in QDD were identified by high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD-low (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. RESULTS: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.

Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

Associations between the signing status of family doctor contract services and cervical cancer screening behaviors: a cross-sectional study in Shenzhen, China.

BACKGROUND: As a core part of the primary healthcare system, family doctor contract services (FDCS) may help healthcare providers promote cervical cancer screening to the female population. However, evidence from population-based studies remains scant. This study aimed to investigate the potential associations between the signing status of FDCS and cervical cancer screening practices in Shenzhen, China. METHODS: A cross-sectional survey among female residents was conducted between July to December 2020 in Shenzhen, China. A multistage sampling method was applied to recruit women seeking health services in community health service centers. Binary logistic regression models were established to assess the associations between the signing status of FDCS and cervical cancer screening behaviors. RESULTS: Overall, 4389 women were recruited (mean age: 34.28, standard deviation: 7.61). More than half (54.3%) of the participants had signed up with family doctors. Women who had signed up for FDCS performed better in HPV-related knowledge (high-level rate: 49.0% vs. 35.6%, P<0.001), past screening participation (48.4% vs. 38.8%, P<0.001), and future screening willingness (95.9% vs. 90.8%, P<0.001) than non-signing women. Signing up with family doctors was marginally associated with past screening participation (OR: 1.13, 95%CI: 0.99-1.28), which tended to be robust among women with health insurance, being older than 25 years old at sexual debut, using condom consistently during sexual intercourse, and with a low level of HPV related knowledge. Similarly, signing up with family doctors was positively associated with future screening willingness (OR: 1.68, 95%CI: 1.29-2.20), which was more pronounced among women who got married and had health insurance. CONCLUSIONS: This study suggests that signing up with family doctors has positive associations with cervical cancer screening behaviors among Chinese women. Expanding public awareness of cervical cancer prevention and FDCS may be a feasible way to achieve the goal of cervical cancer screening coverage.

Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy by targeting the lncRNA Gm41268/PRLR pathway.

BACKGROUND: Astragalus polysaccharide (APS) is a major bioactive component of the Chinese herb astragalus, with well-established protective effects on the kidney. However, the effect of APS on diabetic nephropathy (DN) is unclear. METHODS: Long non-coding RNA (lncRNA) expression profiles in kidney samples from control, db/db, and APS-treated db/db mice were evaluated using RNA high-throughput sequencing techniques. Additionally, rat renal tubular epithelial (NRK-52E) cells were cultured in high glucose (HG) media. We inhibited the expression of Gm41268 and prolactin receptor (PRLR) by transfecting NRK-52E cells with Gm41268-targeting antisense oligonucleotides and PRLR siRNA. RESULTS: We found that APS treatment reduced 24-h urinary protein levels and fasting blood glucose and improved glucose intolerance and pathological renal damage in db/db mice. Furthermore, APS treatment enhanced autophagy and alleviated fibrosis in the db/db mice. We identified a novel lncRNA, Gm41268, which was differentially expressed in the three groups, and the cis-regulatory target gene PRLR. APS treatment induced autophagy by reducing p62 and p-mammalian target of rapamycin (mTOR) protein levels and increasing the LC3 II/I ratio. Furthermore, APS alleviated fibrosis by downregulating fibronectin (FN), transforming growth factor-ß (TGF-ß), and collagen IV levels. In addition, APS reversed the HG-induced overexpression of Gm41268 and PRLR. Reduction of Gm41268 decreased PRLR expression, restored autophagy, and ameliorated renal fibrosis in vitro. Inhibition of PRLR could enhance the protective effect of APS. CONCLUSIONS: In summary, we demonstrated that the therapeutic effect of APS on DN is mediated via the Gm41268/PRLR pathway. This information contributes to the exploration of bioactive constituents in Chinese herbs as potential treatments for DN.

Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2.

Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway.

Glycoside constituents with various antioxidant effects from fresh Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR), an edible and medicinal material, is widely cultivated in desert regions of Eastern and Western Asia, Europe, and North Africa. Ten glycoside constituents 1-10 including one new songaricumone A (1) were isolated from the fresh C. songaricum. Their structures were elucidated by comprehensive NMR data analysis. Further, various antioxidant effects of isolated compounds (1-3 and 5-10) were comprehensively and comparatively investigated. In conclusion, it is obvious that different glycosides vary significantly toward different sources of free radicals, which are attributed to different aglycones and substituted positions of sugar unit in structures.

Association of stress management skills and stressful life events with allergy risk: a case-control study in southern China.

BACKGROUND: Psychosocial stress and stressful life events are known to aggravate allergic diseases. Less is known about the impact of stress management skills on allergies. Here we sought to determine whether stress management skills are associated with the allergies and to assess the combined effects of stress management skills and stressful events on allergy risk. METHODS: A survey on risk factors for self-reported allergic diseases was carried out among 28,144 southern Chinese people; 14 stressful life events and 8 stress management skills were retrospectively recorded in a case-control setting with multivariate logistic regression analysis. Multiplicative and additive interactions between stressful events and stress management skills were evaluated. RESULTS: Stressful events significantly increased allergy risk. The odds ratio (OR) for allergies was 1.65 (95% confidence interval CI, 1.41-1.93) for those reporting one or two stressful events and 3.10 (95% CI, 2.55-3.79) for those reporting more than three stressful events compared to participants without stressful events. Stress management skills were adversely associated with allergic risk for people experiencing stressful events (OR, 0.71; 95% CI, 0.53-0.97) when adjusted demographically, particularly "concentrate on pleasant thoughts at bedtime" (OR, 0.67; 95% CI, 0.51-0.89), "pace myself to prevent tiredness" (OR, 0.67; 95% CI, 0.54-0.83), "get enough sleep" (OR, 0.48; 95% CI, 0.32-0.72) and "take some time for relaxation each day" (OR, 0.55; 95% CI, 0.37-0.80). But in people without stressful events, no association was observed. There was a significant linear trend for allergy risk from good stress management skills with no stressful events to poor stress management skills with stressful events (P < 0.001), with significant interaction in additive models (P = 0.006). CONCLUSIONS: There are independent and antagonistic combined associations of stressful life events and stress management skills with allergy risk. The data supports the use of stress management skills in managing allergic disease among people with stressful life events.

lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA-21.

microRNA-21 (miRNA-21) is a well-characterized oncogenic miRNA in human cancers. In the present study, we found that miRNA-21 was upregulated, while long noncoding RNA Mortal Obligate RNA Transcript (lncRNA MORT), which has been reported to be silenced in 16 types of cancers, was downregulated in tumor tissues than in adjacent healthy tissues of patients with ovarian carcinoma. Expression of lncRNA MORT in tumor tissues was found to be significantly affected by tumor size but not by tumor metastasis. Expression levels of lncRNA MORT and miRNA-21 were significantly and inversely correlated in both tumor tissues and adjacent healthy tissues. Overexpression of lncRNA MORT inhibited miRNA-21, while miRNA-21 overexpression failed to significantly affect lncRNA MORT expression. Overexpression of lncRNA MORT inhibited, while miRNA-21 overexpression promoted the proliferation of cells of ovarian cancer cell lines. In addition, miRNA-21 overexpression partially reversed the inhibitory effects of lncRNA MORT overexpression on cancer cell proliferation. However, overexpression of lncRNA MORT showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA MORT was downregulated in ovarian carcinoma and lncRNA MORT overexpression inhibited cancer cell proliferation, possibly by downregulating miRNA-21.

The development and evaluation of a sub-health self-rating scale for university students in China.

BACKGROUND: Sub-health status is defined as declines in vitality, physiological function and capacity for adaptation, but without the presence of clinical or sub-clinical disease. We have developed and evaluated a comprehensive questionnaire, the Sub-Health Self-Rating Scale (SSS), to assess sub-health status in university students. METHOD: The items for the draft questionnaire were discussed in focus groups. The WHOQOL-BREF was selected as the validity reference. From a professional perspective and large sample evaluation, the scale ultimately consisted of 58 items. The reliability and validity of the SSS was examined in undergraduate students and 1000 questionnaires were randomly selected from the samples for expert evaluation. RESULTS: Cronbach's α of the total scale was 0.942. The dimensions of physiological, psychological and social had high reliability: 0.915, 0.856 and 0.850, respectively. Based on scree plot and related theories, there were 10 factors to be extracted. The correlation coefficient between the total scale and sub-scale was high. The dimensions of physiological, psychological and social had high correlations with the total scale: 0.929, 0.803 and 0.774, respectively. The sub-health cut-off point of the total scale was 72; for the physiological field, it was 72; for the psychological field, it was 60; and the social field, it was 56. The fit between the expert evaluation method and the scale method was 0.758. The lower the score, the worse the health condition. CONCLUSION: We established and evaluated a valid instrument (SSS) that encompasses physiological, psychological and social factors to investigate sub-health status. It is short and easy to complete, and therefore suitable for use with undergraduate students.

Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation.

BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not. METHODS: The HBV-infected mouse model was established by hydrodynamic injection of HBV replicative plasmid, and the mice were treated with saline or fucoidan respectively. Besides, we also tested the inhibitory effect of fucoidan against HBV infection in HBV-transfected cell lines. RESULTS: The result showed that fucoidan from Fucus vesiculosus decreased serum HBV DNA, HBsAg and HBeAg levels and hepatic HBcAg expression in HBV-infected mice. Moreover, fucoidan treatment also suppressed intracellular HBcAg expression and the secretion of the HBV DNA as well as HBsAg and HBeAg in HBV-expressing cells. Furthermore, we proved that the inhibitory activity by fucoidan was due to the activation of the extracellular signal-regulated kinase (ERK) pathway and the subsequent production of type I interferon. Using specific inhibitor of ERK pathway abrogated the fucoidan-mediated inhibition of HBV replication. CONCLUSION: This study highlights that fucoidan might be served as an alternative therapeutic approach for the treatment of HBV infection.

The effects of short-term high-fat feeding on exercise capacity: multi-tissue transcriptome changes by RNA sequencing analysis.

BACKGROUND: The effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown. In this study, we aimed to evaluate exercise capacity in mice fed with a high fat diet (HFD) for 3 days and investigate the molecular mechanisms in the early response to high-fat feeding. METHODS: Exercise capacity was assessed by weight-loaded swimming test in mice fed a control diet (10 kcal% fat) or a HFD (60 kcal% fat) for 3 days. Global gene expression of ten important tissues (brain, heart, liver, spleen, lung, kidney, stomach, duodenum, skeletal muscle and blood) was analyzed using RNA Sequencing. RESULTS: A HFD for just 3 days can induce 71% decrease of exercise performance prior to substantial weight gain (P <0.01). Principle component analysis revealed that differential gene expression patterns existed in the ten tissues. Out of which, the brain, spleen and lung were demonstrated to have more pronounced transcriptional changes than other tissues. Biological process analysis for differentially expressed genes in the brain, spleen and lung showed that dysregulation of peripheral and central immune response had been implicated in the early stage of HFD exposure. Neurotransmission related genes and circulatory system process related genes were significantly down-regulated in the brain and lung, respectively. CONCLUSIONS: Our findings provide new insights for the deleterious effects of high-fat feeding, especially revealing that the lung maybe as a new important target attacked by short-term high-fat feeding.

Polysaccharide extracted from Chinese white wax scale ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like symptoms in BALB/c mice.

Atopic dermatitis (AD) is a common inflammatory skin disease with high rates of morbidity and is associated with erythema, pruritus, scaling of affected areas of skin. It is extremely important to introduce a therapeutic agent which has significant anti-inflammatory effect with less side-effect for treatment of AD. This study evaluated the effect of a natural compound from herbal extracts, the crude polysaccharide extracted from the white wax scale (CWPS), on AD-like mice. Repeated applications of 2,4-dinitrochlorobenzene (DNCB) were performed on ear and dorsal skin of BALB/c mice to induce AD-like symptoms and skin lesions. Oral administration of CWPS decreased serum IgE level and limited the infiltration of mast cells and eosinophils to the dermal tissues in the DNCB-induced AD mice. In addition, CWPS reduced Th1 and Th17 responses, leading to an attenuated cutaneous inflammatory response. Furthermore, in vitro study also demonstrated that CWPS limited T cell activation and cytokines (i.e. IFN-γ and IL-17) production induced by DNCB. We conclude that CWPS attenuates DNCB-induced AD-like skin lesion through modulating T cell-elicited immune responses and CD4+ T cell polarization, and could be exploited as a new therapeutic approach for AD.

[Correlation Analyses between Obesity/Overweight and Constitutions of Chinese Medicine/Cardio- vascular Risk Factors in Elderly Residents of a Community in Guangzhou].

Objective To analyze the correlation between obesity/overweight and constitutions of Chinese medicine (CM)/cardiovascular risk factors in elderly residents of Tianhe District Wushan Com- munity, Guangzhou City. Methods Recruited were 1 054 elderly residents (over 60 years), who had free health examinations in Tianhe District Wushan Community of Guangzhou City from October 2014 to September 2015. They were assigned to the obesity group (107 cases) , the overweight group (431 ca- ses) , and the normal weight group (516 cases) according to body mass index (BMI) by randomized sampling. Constitution types of CM were assessed using Classification and Judgment of Constitution Types of CM. Health files were filled in. General indices such as waist circumference, blood pressure, etc., and blood biochemical indicators such as fasting blood glucose, blood lipids, uric acid, blood creati- nine, etc. were detected. The correlation between constitution types of CM and obesity/overweight was analyzed using multivariate Logistic regression analysis. Results Among the 1 054 elderly residents, 75. 62% (797/1 054) of those were of biased constitution and 24. 38% (257/1 054) were of normal consti- tution. Phlegm dampness (247 cases, 23. 43%), yin deficiency (150 cases, 14. 23%), and qi deficiency (136 cases, 12. 90%) constitution were top 3 commonly seen biased constitution types. Multiple Logistic regression analysis showed that the risk of obese/overweight patients of phlegm dampness constitution was 61. 641 times (Cl: 24. 491 -155. 144) and 9. 393 times (Cl: 5. 910 -14. 929) that of subjects of nor- mal constitution respectively (P <0. 01) ; the risk of obese/overweight patients of dampness heat consti- tution was 21. 478 times (Cl: 6. 978 -66. 102) and 4. 505 times ( Cl: 2. 308 -8. 793) that of subjects of normal constitution respectively (P <0. 01) ; the risk of obese/overweight patients of qi deficiency consti- tution was 3.408 times ( Cl:1. 161 -10. 004) and 1. 655 times (Cl: 1. 062 -2. 580) that of subjects of nor- mal constitution respectively (P <0. 05). Compared with normal body weight senile, the incidences of ab- dominal obesity, hypertension, diabetes were obviously higher in obese/overweight senile (P <0. 01 , P < 0. 05). Their values of fasting blood glucose, triglyceride, high-density lipoprotein, and uric acid were ob- viously higher than those in normal body weight senile (P <0. 01). Conclusions Community obese/over- weighed elderly residents have the tendency of phlegm dampness, dampness heat, and qi deficiency constitutions. Compared with the normal body weight senile, they have higher risk of cardiovascular risk factors, and increased risks of suffering from hypertension, diabetes, and dyslipidemia.

Associations between breakfast eating habits and health-promoting lifestyle, suboptimal health status in Southern China: a population based, cross sectional study.

BACKGROUND: Suboptimal health status (SHS) is the intermediate health state between health and disease, refers to medically undiagnosed or functional somatic syndromes, and has been a major global public health challenge. However, both the etiology and mechanisms associated with SHS are still unclear. Breakfast eating behavior is a dietary pattern marker and previous studies have presented evidence of associations between failure to consume breakfast and increased diseases. Accordingly, in view of the significance of breakfast eating behaviors with respect to health status, the associations between breakfast eating habits and healthy lifestyle, SHS require further elucidation. METHODS: A cross-sectional survey was conducted within a clustered sample of 24,159 individuals aged 12-80 years in 2012-13 within the population of Southern China. Breakfast eating habits were categorically defined by consumption frequency ('scarcely, sometimes or always'). Health-promoting lifestyle was assessed via the health-promoting lifestyle profile (HPLP-II). SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). RESULTS: Of the 24,159 participants, the prevalence rates for the 'health' , 'SHS' , and 'disease' were 18.8%, 46.0%, and 35.2%, respectively. Overall, 19.6% of participants reported 'scarce' breakfast eating habits, with frequent breakfast eaters scoring higher on both HPLP-II and SHMS V1.0. After demographic adjustment, regression analyses revealed a significant association between breakfast eating habits and healthy lifestyle (p <0.001). There were lower levels of breakfast consumption regularity amongst individuals with SHS than those with disease. Categorically 'scarce' breakfast eaters were approximately three times more likely to be assigned SHS (OR: 2.745, 95% CI: 2.468-3.053), while infrequent breakfast eaters ('sometimes') were just less than twice as likely to be assessed as being of SHS (OR: 1.731, 95% CI: 1.595-1.879). CONCLUSIONS: Breakfast eating habits are significantly associated with a healthy lifestyle, and appear to be a useful predictor of a healthy lifestyle. Irregular breakfast eating habits are related to an increased risk of SHS; increased breakfast eating frequency may contribute to lowering the prevalence of SHS in Southern China.

Bu-zhong-yi-qi pill alleviate the chemotherapy-related fatigue in 4 T1 murine breast cancer model.

BACKGROUND: Paclitaxel induced fatigue still remains underrecognized and undertreated, partly because of limited understanding of its pathophysiology and lack of effective treatments. This study is aim to evaluate the anti-fatigue effects and mechanism of Bu-Zhong-Yi-Qi pill in murine 4 T1 breast cancer mice were treated with paclitaxel. METHODS: Breast cancer mice established with murine 4 T1 cells were randomly and repectively divided into five groups: negative control group (NC), tumor control group (TC), paclitaxel group (PTX), Bu-Zhong-Yi-Qi pill group (BZYQ) and Bu-Zhong-Yi-Qi pill plus paclitaxel group (BZYQ + PTX). The mice were administered for 21 days. During this period, the tumor volume, body weight and the weight-loaded swimming time were measured. After the last administration, all mice were sacrificed, weighted the tumor, measured immune cell cytokines and oxidative stress indicator. The remaining 10 mice in each group were observed for survival analysis. RESULTS: Treatments with BZYQ + PTX and PTX significantly reduced the rates of tumor volume in comparison with TC starting on the 9th day and the 18th day respectively (P < 0.05-0.01), and presented decreased tumor weight compared to TC (P < 0.05-0.01). Compared with mice in TC group, the median survival time and the average survival time in BZYQ + PTX group, BZYQ group and PTX group were significantly prolonged (P < 0.05-0.01). The swimming time of the BZYQ + PTX group gradually increased, which is longer than the PTX group on Day 14 and Day 21 (P < 0.01). The level of TNF-α was lower in BZYQ + PTX group than PTX group (P < 0.01). The level of SOD activity in BZYQ + PTX group was lower than the NC group (P <0.01), but much higher than the PTX group (P < 0.01). The level of MDA of BZYQ + PTX group was higher than the NC group (P < 0.01), but significant lower than the PTX group (P < 0.01). CONCLUSIONS: BZYQ has the potential of alleviating paclitaxel chemotherapy-related fatigue in 4 T1 breast cancer mice by reducing the serum levels of TNF-α and modulating the level of MDA and the SOD activity.

Nanoplatform based on carbon nanoparticles loaded with doxorubicin enhances apoptosis by generating reactive oxygen species for effective cancer therapy.

At present, due to its wide application and relatively low cost, chemotherapy remains a clinically important cancer treatment option; however, a number of chemotherapeutic drugs have important limitations, such as lack of specificity, high toxicity and side effects, and multi-drug resistance. The emergence of nanocarriers has removed numerous clinical application limitations of certain antitumor chemotherapy drugs and has been widely used in the treatment of tumors with nanodrugs. The present study used carbon nanoparticles (CNPs) as a nanocarrier for doxorubicin (DOX) to form the novel nanomedicine delivery system (CNPs@DOX)was demonstrated by UV-vis and fluorescence spectrophotometry, ζ potential and TEM characterization experiments. The results confirmed the successful preparation of CNPs@DOX nanoparticles with a particle size of 96±17 nm, a wide range of absorption and a negatively charged surface. Furthermore, CNPs@DOX produced more reactive oxygen species and induced apoptosis, and thus exhibited higher cytotoxicity than DOX, which is a small molecule anticancer drug without a nanocarrier delivery system.. The present study provides a strategy for the treatment of tumors with nanomedicine.

Early-life antibiotic exposure promotes house dust mite-induced allergic airway inflammation by impacting gut microbiota and lung lipid metabolism.

Asthma is a chronic inflammatory respiratory disease. Early-life antibiotic exposure is a unique risk factor for the incidence and severity of asthma later in life. Perturbations in microbial-metabolite-immune interaction caused by antibiotics are closely associated with the pathogenesis of allergy and asthma. We investigated the effect of early intervention with common oral antibiotics on later asthma exacerbations and found that different antibiotic exposures can amplify different types of immune responses induced by HDM. Cefixime (CFX) promoted a biased type 2 inflammation, azithromycin (AZM) enhanced Th17 immune response, and cefuroxime axetil (CFA) induced eosinophils recruitment. Moreover, early-life antibiotic exposure can have short- and long-term effects on the abundance, composition, and diversity of the gut microbiota. In the model of CFX-promoted type 2 airway inflammation, fecal metabolomics indicated abnormal lipid metabolism and T cell response. Lipidomic also suggested allergic airway inflammation amplified by CFX is closely associated with abnormal lipid metabolism in lung tissues. Moreover, abnormalities in lipid metabolism-related genes (LMRGs) were found to have cellular heterogeneity be associated with asthma severity by bioinformatics analysis.

Identification of inhibitors from a functional food-based plant Perillae Folium against hyperuricemia via metabolomics profiling, network pharmacology and all-atom molecular dynamics simulations.

Introduction: Hyperuricemia (HUA) is a metabolic disorder caused by purine metabolism dysfunction in which the increasing purine levels can be partially attributed to seafood consumption. Perillae Folium (PF), a widely used plant in functional food, has been historically used to mitigate seafood-induced diseases. However, its efficacy against HUA and the underlying mechanism remain unclear. Methods: A network pharmacology analysis was performed to identify candidate targets and potential mechanisms involved in PF treating HUA. The candidate targets were determined based on TCMSP, SwissTargetPrediction, Open Targets Platform, GeneCards, Comparative Toxicogenomics Database, and DrugBank. The potential mechanisms were predicted via Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) analyses. Molecular docking in AutoDock Vina and PyRx were performed to predict the binding affinity and pose between herbal compounds and HUA-related targets. A chemical structure analysis of PF compounds was performed using OSIRIS DataWarrior and ClassyFire. We then conducted virtual pharmacokinetic and toxicity screening to filter potential inhibitors. We further performed verifications of these inhibitors' roles in HUA through molecular dynamics (MD) simulations, text-mining, and untargeted metabolomics analysis. Results: We obtained 8200 predicted binding results between 328 herbal compounds and 25 potential targets, and xanthine dehydrogenase (XDH) exhibited the highest average binding affinity. We screened out five promising ligands (scutellarein, benzyl alpha-D-mannopyranoside, elemol, diisobutyl phthalate, and (3R)-hydroxy-beta-ionone) and performed MD simulations up to 50 ns for XDH complexed to them. The scutellarein-XDH complex exhibited the most satisfactory stability. Furthermore, the text-mining study provided laboratory evidence of scutellarein's function. The metabolomics approach identified 543 compounds and confirmed the presence of scutellarein. Extending MD simulations to 200 ns further indicated the sustained impact of scutellarein on XDH structure. Conclusion: Our study provides a computational and biomedical basis for PF treating HUA and fully elucidates scutellarein's great potential as an XDH inhibitor at the molecular level, holding promise for future drug design and development.