Astragalus polysaccharide alleviates polycystic ovary syndrome by reducing insulin resistance and oxidative stress and increasing the diversity of gut microbiota.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is frequently accompanied by insulin resistance, oxidative stress (OS), and dyslipidemia. Astragalus polysaccharide (APS)-as a water-soluble heteropolysaccharide-can lower blood sugar and lipid and exert anti-aging effects and thus has been proven to be beneficial to various types of metabolic diseases. However, specific mechanisms of the action of APS on PCOS are yet to be studied. METHODS: Herein, BALB/C female mice aged 3 weeks were randomly divided into three groups (10 mice/group): oil + PBS group, DHEA + PBS group, and DHEA + APS group. Changes in the estrous cycle, ovarian tissue sections, serum levels of the hormone, blood glucose, blood lipid, and OS were studied. The intestinal microbiome was sequenced and Spearman correlation analysis was used to analyze the correlation between serum metabolic indexes and microflora. RESULTS: The results revealed that APS treatment ameliorated insulin resistance, OS, and dyslipidemia in PCOS mice. The results of 16S rDNA sequencing indicated that there were significant differences in the composition and diversity of intestinal microorganisms between DHEA and APS treatments. Firmicutes, Lachnospiraceae, Bacilli, Lactobacillaceae, and Lachnospiraceae_NK4A13_group were abundant in the oil + PBS group. Bacteroidota and Muribaculaceae were enriched in the DHEA + PBS group, while Rikenellaceae, Odoribacter, and Marinifilaceae were enriched in the DHEA + APS group. Furthermore, Spearman correlation analysis showed that there were close interactions and correlations between intestinal bacteria and indicators of blood glucose, blood lipids, steroid hormones, and OS in PCOS mice. CONCLUSIONS: Overall, the study showed that APS improved PCOS in mice by correcting serum metabolic disorders and increasing microbiome diversity, which may provide insight into understanding the pathogenesis and be a beneficial intervention for PCOS.

miR-542-5p targets c-myc and negates the cell proliferation effect of SphK1 in intestinal epithelial cells.

Intestinal epithelial barrier defects occur commonly during a variety of pathological conditions, though their underlying mechanisms are not completely understood. Sphingosine-1-phosphate (S1P) has been shown to be a critical regulator of proliferation and of maintenance of an intact intestinal epithelial barrier, as is also sphingosine kinase 1 (SphK1), the rate-limiting enzyme for S1P synthesis. SphK1 has been shown to modulate its effect on intestinal epithelial proliferation through increased levels of c-myc. We conducted genome-wide profile analysis to search for differential microRNA expression related to overexpressed SphK1 demonstrating adjusted expression of microRNA 542-5p (miR-542-5p). Here, we show that miR-542-5p is regulated by SphK1 activity and is an effector of c-myc translation that ultimately serves as a critical regulator of the intestinal epithelial barrier. miR-542-5p directly regulates c-myc translation through direct binding to the c-myc mRNA. Exogenous S1P analogs administered in vivo protect murine intestinal barrier from damage due to mesenteric ischemia reperfusion, and damaged intestinal tissue had increased levels of miR-542-5p. These results indicate that miR-542-5p plays a critical role in the regulation of S1P-mediated intestinal barrier function, and may highlight a novel role in potential therapies.

The effect of magnesium alone or its combination with other supplements on the markers of inflammation, OS and metabolism in women with polycystic ovarian syndrome (PCOS): A systematic review.

The objective of this systematic review is to synthesize the available evidence on the effectiveness of magnesium supplements on the markers of inflammation, oxidative stress (OS), and metabolism in PCOS patients and to provide a basis for its clinical treatment. Electronic databases (PubMed, Cochrane Library databases, Embase, Web of science, CMB, CNKI, VIP, Wan Fang and ClinicalTrials.gov) were searched from their inception until January 2022. Randomized controlled trials (RCTs) for PCOS undergoing therapy with magnesium supplementation alone or in combination with other agents. The primary outcomes were the markers of blood glucose and OS.363 patients from nine RCTs were included in the current systematic review. Four of the nine studies reported the effects of magnesium supplementation alone on OS or metabolic markers in women with PCOS. Whilemagnesium supplementation alone did not show any significant improvement in the markers of inflammation, OS or metabolism in PCOS, seven of the nine articles reported the effect of magnesium co-supplementation on OS or metabolic markers in PCOS patients. Magnesium combined with vitamin E or zinc-calcium-vitamin D significantly improved glucose and lipid metabolism in PCOS patients. Magnesium intake alone did not lead to a significant improvement in the markers of OS, blood glucose, or serum lipids in PCOS. However, magnesium combined with other supplements (vitamin E, zinc, zinc-calcium-vitamin D) significantly improved serum hs-CRP, insulin, HOMA-IR, TG, TC levels, and the improvement in OS markers was inconclusive. The effect of magnesium and melatonin supplementation on the markers of metabolism needs to be further verified. System Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42022303410.

Role of Pyroptosis in Gynecological Oncology and Its Therapeutic Regulation.

With the continuous advances in molecular biotechnology, many new cell death methods have been discovered. Pyroptosis is a programmed cell death process that differs from apoptosis and autophagy in cell morphology and function. Compared with apoptosis and autophagy, pyroptosis is primarily mediated by intracellular inflammasome and gasdermin D of the gasdermin protein family and involves the release of numerous inflammatory factors. Pyroptosis has been found to be involved in the occurrence and development of infectious diseases and other diseases involving the nervous system and the cardiovascular system. Recent studies have also reported the occurrence of pyroptosis in tumor cells. Accordingly, exploring its effect on tumors has become one of the research hotspots. Herein, recent research progress on pyroptosis is reviewed, especially its role in the development of gynecological tumors. As the pathogenesis of gynecological tumor is better understood, new targets have been introduced for the prevention and clinical treatment of gynecological tumors.

UPLC-MS-Based Serum Metabolic Profiling Reveals Potential Biomarkers for Predicting Propofol Responsiveness in Females.

Although previous studies have shown that certain factors interfere with the sensitivity of propofol, the mechanisms for interindividual variability in response to propofol remain unclear. This study aimed to screen the metabolites to predict patients' sensitivity to propofol and to identify metabolic pathways to explore possible mechanisms associated with propofol resistance. Sera from 40 female patients undergoing elective hysteroscopic surgery in a prospective cohort propofol study were obtained before the administration of propofol. The patients' responsiveness to propofol was differentiated based on propofol effect-site concentration. Serum samples from two sets, a discovery set (n = 24) and an independent validation set (n = 16), were analyzed using ultraperformance liquid chromatography coupled with mass spectrometry based untargeted metabolomics. In the discovery set, 494 differential metabolites were screened out, and then 391 potential candidate biomarkers with the area under receiver operating characteristic curve >0.80 were selected. Pathway analysis showed that the pathway of glycerophospholipid metabolism was the most influential pathway. In the independent validation set, six potential biomarkers enabled the discrimination of poor responders from good and intermediate responders, which might be applied to predict propofol sensitivity. The mass spectrometry data are available via MetaboLights (http://www.ebi.ac.uk/metabolights/login) with the identifier MTBLS2311.

miR­351­5p aggravates lipopolysaccharide­induced acute lung injury via inhibiting AMPK.

Inflammation and oxidative stress have indispensable roles in the development of acute lung injury (ALI). MicroRNA (miRNA/miR)­351­5p was initially identified as a myogenesis­associated miRNA; however, its role in lipopolysaccharide (LPS)­induced ALI remains unclear. The aim of the present study was to investigate the role and potential mechanisms of miR­351­5p in ALI. ALI was induced through a single intratracheal injection of LPS for 12 h, and miR­351­5p agomir, antagomir or their corresponding negative controls were injected into the tail vein before LPS stimulation. Compound C, 2',5'­dideoxyadenosine and H89 were used to inhibit AMP­activated protein kinase (AMPK), adenylate cyclase and protein kinase A (PKA), respectively. miR­351­5p levels in the lungs were significantly increased in response to LPS injection. miR­351­5p antagomir alleviated, while miR­351­5p agomir aggravated LPS­induced oxidative stress and inflammation in the lungs. The present results also demonstrated that miR­351­5p antagomir attenuated LPS­induced ALI via activating AMPK, and that the cAMP/PKA axis was required for the activation of AMPK by the miR­351­5p antagomir. In conclusion, the present study indicated that miR­351­5p aggravated LPS­induced ALI via inhibiting AMPK, suggesting that targeting miR­351­5p may help to develop efficient therapeutic approaches for treating ALI.

Anti-F4/80 treatment attenuates Th2 cell responses: Implications for the role of lung interstitial macrophages in the asthmatic mice.

Lung interstitial macrophages (IMs) can be polarized towards an alternative activation phenotype in ovalbumin (OVA)-induced asthmatic mice. However, the role of alternative activation of lung IMs in Th2 cell responses in the asthmatic murine is still unclear. Here, we leverage an anti-F4/80 treatment which has been shown to selectively deplete IMs in mice and investigate how this treatment modulates Th2 cell responses in lung and whether the modulation is dependent on lung IMs in murine models of asthma. We show that anti-F4/80 treatment alleviates Th2 cell responses in mice immunized and challenged with OVA or house dust mite (HDM). The anti-F4/80 treatment does not target lung alveolar macrophages (AMs) in OVA-induced asthmatic mice or impact the abundance of other immune cell types, including B cells, T cells, and NK cells in wild-type mice. However, this treatment does inhibit the expression of polarized markers of alternatively activated macrophages, including arginase-1, Ym-1, and Fizz-1 in the lung tissues from OVA-induced asthmatic mice. Furthermore, we find that the inhibitory effects of anti-F4/80 treatment on Th2 cell responses can be reversed upon adoptive transfer of lung IMs. Taken together, our data show that anti-F4/80 treatment attenuates Th2 cell responses, which is at least partially related to depletion of lung IMs in murine models of asthma. This suggests that targeted lung IMs may provide a potential therapeutic protocol for the treatment of asthmatics.

MicroRNA-30d-5p ameliorates lipopolysaccharide-induced acute lung injury via activating AMPKα.

OBJECTIVES: Acute lung injury (ALI) is a devastating lung disease characterized by uncontrolled pulmonary inflammation and oxidative stress. Currently, no effective therapeutic strategies are available for ALI and its prognosis remains poor. The present study aims to investigate the role and potential mechanism of microRNA-30d-5p (miR-30d-5p) in the progression of ALI. METHODS: Mice were intravenously treated with miR-30d-5p agomir, antagomir or their respective controls for 3 consecutive days and then were exposed to a single intratracheal injection of lipopolysaccharide (LPS) for 12 h at a dosage of 5 mg/kg to induce ALI. To inhibit adenosine monophosphate-activated protein kinase α (AMPKα) or phosphodiesterase 4 D (PDE4D), compound C (CpC) and rolipram were used. RESULTS: miR-30d-5p expression in the lungs was significantly inhibited by LPS treatment. miR-30d-5p agomir significantly alleviated, while miR-30d-5p antagomir aggravated pulmonary inflammation, oxidative damage, and dysfunction in ALI mice. Besides, we found that miR-30d-5p agomir ameliorated LPS-induced ALI via activating AMPKα and that the inhibition of AMPKα by CpC completely abolished these beneficial effects of miR-30d-5p agomir. Further findings validated that PDE4D downregulation was required for the activation of AMPKα by miR-30d-5p agomir. CONCLUSION: miR-30d-5p ameliorates LPS-induced ALI via activating AMPKα and it is a valuable therapeutic candidate in the treatment of ALI.

3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study.

BACKGROUND: The consequences of COVID-19 in those who recover from acute infection requiring hospitalisation have yet to be clearly defined. We aimed to describe the temporal trends in respiratory outcomes over 12 months in patients hospitalised for severe COVID-19 and to investigate the associated risk factors. METHODS: In this prospective, longitudinal, cohort study, patients admitted to hospital for severe COVID-19 who did not require mechanical ventilation were prospectively followed up at 3 months, 6 months, 9 months, and 12 months after discharge from Renmin Hospital of Wuhan University, Wuhan, China. Patients with a history of hypertension; diabetes; cardiovascular disease; cancer; and chronic lung disease, including asthma or chronic obstructive pulmonary disease; or a history of smoking documented at time of hospital admission were excluded at time of electronic case-note review. Patients who required intubation and mechanical ventilation were excluded given the potential for the consequences of mechanical ventilation itself to influence the factors under investigation. During the follow-up visits, patients were interviewed and underwent physical examination, routine blood test, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide [DLCO]; forced expiratory flow between 25% and 75% of forced vital capacity [FVC]; functional residual capacity; FVC; FEV1; residual volume; total lung capacity; and vital capacity), chest high-resolution CT (HRCT), and 6-min walk distance test, as well as assessment using a modified Medical Research Council dyspnoea scale (mMRC). FINDINGS: Between Feb 1, and March 31, 2020, of 135 eligible patients, 83 (61%) patients participated in this study. The median age of participants was 60 years (IQR 52-66). Temporal improvement in pulmonary physiology and exercise capacity was observed in most patients; however, persistent physiological and radiographic abnormalities remained in some patients with COVID-19 at 12 months after discharge. We found a significant reduction in DLCO over the study period, with a median of 77% of predicted (IQR 67-87) at 3 months, 76% of predicted (68-90) at 6 months, and 88% of predicted (78-101) at 12 months after discharge. At 12 months after discharge, radiological changes persisted in 20 (24%) patients. Multivariate logistic regression showed increasing odds of impaired DLCO associated with female sex (odds ratio 8·61 [95% CI 2·83-26·2; p=0·0002) and radiological abnormalities were associated with peak HRCT pneumonia scores during hospitalisation (1·36 [1·13-1·62]; p=0·0009). INTERPRETATION: In most patients who recovered from severe COVID-19, dyspnoea scores and exercise capacity improved over time; however, in a subgroup of patients at 12 months we found evidence of persistent physiological and radiographic change. A unified pathway for the respiratory follow-up of patients with COVID-19 is required. FUNDING: National Natural Science Foundation of China, UK Medical Research Council, and National Institute for Health Research Southampton Biomedical Research Centre. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Development of preparation process of icaritin-coix seed oil microemulsion based on quality by design concept].

To optimize the formulation and preparation process of icaritin-coix seed oil microemulsion(IC-MEs) based on quality by design(QbD) concept. IC-MEs were prepared by water titration. Firstly, the risk factors that may affect the quality of IC-MEs were evaluated. Then Plackett-Burman design was used to screen out prescription factors and process parameters that had a significant effect on the indicators. Finally, Box-Behnken design was used to optimize the prescription ratio of IC-MEs. Through the risk assessment and Plackett-Burman design, three formulation factors [drug loading efficiency, the ratio of mixed-oil(coix seed oil-Glycerol tributyrate) to mixed-surfactant(HS15-RH40) and water addition] were determined as the key factors affecting IC-MEs. The regression model established by Box-Behnken design had a good predictability. The optimal formula was as following: the drug loading efficiency of 0.92%, the ratio of mixed-oil(coix seed oil-glycerol tributyrate) to mixed-surfactant(HS15-RH40) of 4∶6, and the water addition of 5.7 mL. According to this prescription, IC-MEs were prepared, and its encapsulation efficiency after 1 week was 92.45%±1.00%. Therefore, the stability of IC-MEs could be improved by optimizing prescription and process parameters of IC-MEs based on the QbD concept, which can provide certain reference value for the future development of IC-MEs.

Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis.

Recent reports have showed that a proportion of patients with Coronavirus Disease 2019 (COVID-19) presented elevated leukocyte count. Clinical data about these patients is scarce. We aimed to evaluate the clinical findings of patients with COVID-19 who have increased leukocyte at admission. We retrospectively collected the clinical data on the 52 patients who have increased leukocyte count at admission from the 619 patients with confirmed COVID-19 who had pneumonia with abnormal features on chest CT scan in Renmin Hospital of Wuhan University in Wuhan, China, from February 3 to March 3, 2020. The mean age of the 52 patients with increased leukocyte count was 64.7 (SD 11.4) years, 32 (61.5%) were men and 47 (90.4%) had fever. Compared with the patients with non-increased leukocyte count, the patients with increased leukocyte count were significantly older (P < 0.01), were more likely to have underlying chronic diseases (P < 0.01), more likely to develop critically illness (P < 0.01), more likely to admit to an ICU (P < 0.01), more likely to receive mechanical ventilation (P < 0.01), had higher rate of death (P < 0.01) and the blood levels of neutrophil count and the serum concentrations of CRP and IL-6 were significantly increased, (P < 0.01). The older patients with COVID-19 who had underlying chronic disorders are more likely to develop leukocytosis. These patients are more likely to develop critical illness, with a high admission to an ICU and a high mortality rate.

Impact of Anxiety or Depression Symptoms on Propofol Requirements for Sedation in Females: A Prospective Cohort Study.

Mental disorders are thought to affect various clinical outcomes during the perioperative period. Among them, anxiety and depression are 2 of the most common types. However, the impacts of anxiety or depression on propofol requirements remain unclear. This study aimed to investigate the effects of anxiety or depression symptoms on the propofol requirements for sedation in females. This study recruited female patients aged 18 to 65 years, with American Society of Anesthesiologists physical status classification of 1 to 2, who were scheduled for hysteroscopic surgery under propofol-based intravenous anesthesia. The day before surgery, the Hospital Anxiety and Depression Scale (HADS) was used to assess the symptoms of anxiety and depression within the past 6 months. Target-controlled propofol was gradually titrated to achieve 3 desired levels of sedation: Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S) score 3, MOAA/S score 1, and MOAA/S score 1 and Narcotrend Index <65. The effect-site concentration of propofol correlated with HADS-Anxiety scores for the sedation levels of MOAA/S 3 and 1 (r = .249, P = .008; and r = .190, P = .045, respectively). However, the propofol requirements did not correlate with HADS-Depression scores at any sedation level. In conclusion, female patients with anxiety symptoms, but not depression symptoms, required a higher dose of propofol for sedation in hysteroscopy.

Blockade of CD40L inhibits immunogenic maturation of lung dendritic cells: Implications for the role of lung iNKT cells in mouse models of asthma.

Some studies have shown that maturation of dendritic cells (DCs) is modulated directly by pathogen components via pattern recognition receptors such as Toll-like receptors, but also by signal like CD40 ligand (CD40 L or CD154) mediated by activated T cells. Several reports indicate that invariant natural killer T (iNKT) cells up-regulate CD40 L upon stimulation and thereby induce activation and maturation of DCs through crosslink with CD40. Our previous findings indicated that iNKT cells promote Th2 cell responses through the induction of immunogenic maturation of lung DCs (LDCs) in the asthmatic murine, but its mechanism remains unclear. Therefore, we investigated the immunomodulatory effects of blockade of CD40 L using anti-CD40 L treatment on Th2 cell responses and immunogenic maturation of LDCs, and further analyzed whether these influences of blockade of CD40 L were related to lung iNKT cells using iNKT cell-deficient mice and the combination treatment of specific iNKT cell activation with anti-CD40 L treatment in murine models of asthma. Our findings showed that blockade of CD40 L using anti-CD40 L treatment attenuated Th2 cell responses in wild-type (WT) mice, but not in CD1d-deficient mice sensitized and challenged with ovalbumin (OVA) or house dust mite (HDM). Meanwhile, blockade of CD40 L down-regulated immunogenic maturation of LDCs in WT mice, but not in CD1d-deficient mice sensitized and challenged with OVA. Additionally, agonistic anti-CD40 treatment reversed the inhibitory effects of anti-CD40 L treatment on Th2 cell responses and LDC activation in an OVA-induced mouse model of asthma. Furthermore, LDCs from asthmatic mice treated with anti-CD40 L could significantly reduce the influence on Th2 cell responses in vivo and in vitro. Finally, α-Galactosylceramide plus anti-CD40 L treatment stimulated lung iNKT cells, but suppressed Th2 cell responses in the asthmatic mice. Taken together, our data raise an evidence that blockade of CD40 L attenuates Th2 cell responses through the inhibition of immunogenic maturation of LDCs, which may be at least partially related to lung iNKT cells in murine models of asthma.

Investigation of the mechanism of incompatible herb pair gansui-gancao-induced hepatotoxicity and nephrotoxicity and the attenuated effect of gansuibanxia decoction by UHPLC-FT-ICR-MS-based plasma metabonomic analysis.

Gansui-Gancao is one of the "eighteen incompatible herb pairs" which was recorded 2000 years ago according to TCM (Traditional Chinese Medicine) theory for their toxicity when using together. Nevertheless, Gansuibanxia decoction contained the herb pair have satisfactory effect on the treatment of cancerous ascites, pericardial effusion, etc. The present study aimed to investigate the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction using UHPLC-FT-ICR-MS in a metabonomic perspective. Rats were divided into four groups administrated with different herb combination extracts for successive 14 days. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to plot the metabolic state and screen the potential biomarkers in plasma. A total of 20 biomarkers contributed to the separation of Gansui-Gancao group and control group were tentatively identified mainly involved in 7 metabolic pathways related to hepatotoxicity and nephrotoxicity. The contents of these biomarkers were adjusted to normal levels in Gansuibanxia decoction group. Thus, the results of our study reveled the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction in a metabonomic perspective and it's valuable for better understanding the "eighteen incompatible madicaments" of TCM theory.

Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion.

BACKGROUND: To date, mechanisms of intestinal immunoglobulin (Ig) dysfunction following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death 1 (PD-1) is associated with immune responses of lymphocytes. AIM: We aimed to verify the hypothesis that activation of PD-1 may improve intestinal immune dysfunction by regulating IL-10/miR-155 production after intestinal IR injury. METHODS: Intestinal I/R injury was induced in mice by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-L1 fusion Ig, anti-interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer's patches (PP) CD4+ cells were measured. MiR-155 levels, tumor necrosis factor (TNF)-α and IL-1ß concentration, and activation-induced cytidine deaminase (AID), a key enzyme for intestinal immune antibodies, in PP tissues were measured, respectively. Importantly, the production and cecal bacteria-binding capacity of IgA and IgM were detected. RESULTS: Intestinal I/R led to decreased PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then decreased miR-155 levels, and subsequently promoted AID expression and reduced TNF-α, IL-1ß concentration. Upregulation of AID improved the disruptions of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal immune defense. CONCLUSION: Activation of PD-1 with PD-L1 Ig relieves intestinal immune defensive injury through IL-10/miR-155 pathway following intestinal I/R attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of intestinal barrier and immunity.

Invariant natural killer T cells promote immunogenic maturation of lung dendritic cells in mouse models of asthma.

Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, coculture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data showed that iNKT cell deficiency could downregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from a mouse model of asthma. However, elevated activation of iNKT cells by α-galactosylceramide and adoptive transfer of iNKT cells could upregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from mouse models of asthma. Meanwhile, iNKT cells significantly influenced the function of LDCs, markedly enhancing Th2 responses in vivo and in vitro. In addition, iNKT cell can induce LDCs expression of CD206 and RELM-α, reflecting alternative activation of LDCs in a mouse model of asthma. α-Galactosylceramide treatment significantly enhanced expression of CD40L of lung iNKT cells from a mouse model of asthma, and the coculture experiment of LDCs with iNKT cells showed that the blockade of CD40L strongly suppressed surface maturation markers and proinflammatory cytokine production by LDCs. Our data suggest that iNKT cells can promote immunogenic maturation of LDCs to enhance Th2 responses in mouse models of asthma.

Bakuchiol inhibits cell proliferation and induces apoptosis and cell cycle arrest in SGC-7901 human gastric cancer cells.

PURPOSE: The main purpose of the present study was to evaluate the antiproliferative activity of bakuchiol in human gastric tumor cell line (SGC-7901) along with an effort to demonstrate its mode of action. METHODS: he effect of the compound on cell viability was evaluated by MTT assay. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution. RESULTS: The results revealed that bakuchiol exerted potent, dose-dependent as well as time-dependent growth inhibitory effects in SGC-7901 cell proliferation with IC50 values of 58.4, 42.3 and 32.5 µM at 12, 24 and 48 hrs time intervals, respectively. On treatment with 10, 50 and 100 µM dose of bakuchiol for 48 hrs, phase contrast microscope revealed that the cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM of bakuchiol, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Bakuchiol also induced sub-G1 cell cycle arrest in a dose-dependent manner. CONCLUSION: The current findings reveal that bakuchiol is a potent cytotoxic agent against gastric cancer cells and its cytotoxicity is mediated through induction of apoptosis and sub-G1 cell cycle arrest.

Highly effective permeability and antifouling performances of polypropylene non-woven fabric membranes modified with graphene oxide by inkjet printing and immersion coating methods.

In the current study, graphene oxide (GO)-modified polypropylene non-woven fabric (PP-NWF) membranes were prepared via inkjet printing and immersion coating methods. Scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurements, pure water permeation (JPWP) and protein adsorption were tested to evaluate the impact of the GO nanosheet on the characteristics and performance of modified PP-NWF membranes. The results showed that the exfoliated GO nanosheets uniformly deposited on the membrane surface and firmly embedded into the interlaced fibers, resulting in the improvement of membrane hydrophilicity, permeability and antifouling properties comparing with original PP-NWF membranes. The GO-printed and GO-coated membranes had 113 and 188% higher fluxes, and 70.95 and 75.74% lower protein adsorptions than the original PP-NWF membranes, respectively. After cross-linked treatment, ultrasound processing was conducted to evaluate the stability of the modified PP-NWF membranes. The results demonstrated that there was almost no decrease in permeation after ultrasonic treatment indicating that the cross-linking treatment could enhance the immobilization of the GO nanosheets on and into the modified membranes.

Sphingosine kinase 1 overexpression stimulates intestinal epithelial cell proliferation through increased c-Myc translation.

Sphingosine-1-phosphate (S1P), through mechanisms that are not completely understood, is shown to modulate cellular proliferation, which is critically important for maintaining the integrity of intestinal epithelium. Here, we show that increased S1P promotes proliferation in intestinal epithelial cells. We found that overexpression of sphingosine kinase 1 (SphK1), the rate-limiting enzyme for S1P synthesis, significantly increased cell proliferation and that this occurred through enhanced expression of c-Myc. Further, we found that the increased pattern of expression of c-Myc occurred predominantly due to its increased translation. The overexpressed SphK1 led to increased checkpoint kinase 2 and enhanced HuR phosphorylation which allowed for increased translation of c-Myc mRNA through HuR binding at the 3'-untranslated regions. Our findings demonstrate that S1P modulates intestinal cell proliferation and provides new insights as to the mechanistic actions of SphK1 and S1P in maintaining intestinal epithelial homeostasis.

Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers.

BACKGROUND: Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs. METHODS: By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs. RESULTS: In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one. CONCLUSIONS: The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.