Effect of aqueous extract of seed of broccoli on inflammatory cytokines and Helicobacter pylori infection: a randomized, double-blind, controlled trial in patients without atrophic gastritis.

The purpose of this study was to investigate the anti-inflammatory effect of an aqueous extract of seed of broccoli (AESB) in Helicobacter pylori (HP)-infected patients without atrophic gastritis. This was a double-centre, randomized, double-blind, controlled study. A total of 110 HP-infected subjects were randomized to receive either AESB or placebo for 2 months. Inflammatory cytokine (IL-8, IFN-γ, TNF-α, CRP, IL-17A, IL-1ß, IL-18), pepsinogen I, II (PG I, PG II), and gastrin-17 (G-17) measurements and 13C-urea breath tests were performed at baseline and at 60 days. At 60 days, there was no significant difference in any of the inflammatory cytokines, pepsinogen or gastrin between the two groups. However, IL-8, IFN-γ, PG I, PG I/PG II ratio (PGR), and G-17 were reduced by 9.02 pg/mL, 5.08 pg/mL, 24.56 ng/mL, 1.75 and 0.3 pmol/L, respectively, in the AESB group compared with baseline (all P < 0.05). The HP eradication rates in the AESB group and placebo group were 11.11 and 3.70% at 60 days, respectively (P > 0.05). No treatment-related adverse events were reported. Thus, AESB may reduce the risk of gastric mucosal lesions and decrease the risk of gastric cancer by relieving inflammatory cytokines. The safety profile of AESB was satisfactory. This study is registered with the Chinese Clinical Trials Registry (Registration No. ChiCTR2100054249).

NLRP3 inflammasome is involved in ambient PM2.5-related metabolic disorders in diabetic model mice but not in wild-type mice.

AIMS: To explore the role of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in ambient fine particulate matter (PM2.5)-related metabolic disorders. METHODS: In this study, the C57BL/6 and db/db mice were exposed to concentrated PM2.5 or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 12 weeks. Indices of lipid metabolism, glucose metabolism, insulin sensitivity, and protein expression of NLRP3 inflammasome in visceral adipose tissue (VAT) were measured, respectively. RESULTS: The results showed that PM2.5 exposure increased circulatory insulin, triglycerides (TG), and total cholesterol (TC), and decreased high-density lipoprotein (HDL) in both C57BL/6 and db/db mice. The levels of NLRP3-related circulatory inflammatory cytokines including both interleukin (IL)-18 and IL-1ß in serum were increased in the PM2.5-exposed mice and accompanied by the elevation in fasting blood glucose and insulin. The results also showed that exposure to PM2.5 promoted the activation of NLRP3, pro-caspase-1, caspase-1, and apoptosis-associated speck-like protein containing CARD (ASC), simultaneously accompanied by the increase of IL-18 and IL-1ß expression in VAT, but the statistically significant difference only found in the db/db mice, not in C57BL/6 mice. CONCLUSION: The activation of NLRP3 inflammasome might be not the main mechanism of PM2.5-related metabolic disorders in wide type mice but it partly mediated the exacerbation of metabolic disorders in diabetic model mice.

Parental PM2 .5 exposure changes Th17/Treg cells in offspring, is associated with the elevation of blood pressure.

Epidemiological evidences have indicated that fine particulate matter (PM2.5 ) exposure is associated with the occurrence and development of hypertension. The present study aims to explore the effects of parental PM2.5 exposure on blood pressure in offspring and elucidate the potential mechanism. The parental male and female C57BL/6 mice were exposed to concentrated PM2.5 or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 16 weeks. At week 12, the mice were assigned to breed offspring. The male offspring mice were further exposed to PM2.5 or FA as above method. During the parental exposure, the average PM2.5 concentration was 133.7 ± 53.32 µg/m3 in PM chamber, whereas the average concentration in FA chamber was 9.4 ± 0.23 µg/m3 . Similarly, during the offspring exposure, the average concentration in PM and FA chamber were 100.76 ± 26.97 µg/m3 and 9.15 ± 0.15 µg/m3 , respectively. The PM2.5 -exposed offspring mice displayed the elevation of blood pressure, the increase of angiotensin II (Ang II), the decrease of angiotensin converting enzyme 2 (ACE2) and Ang (1-7) in serum when compared with the FA-exposed offspring mice. The similar results displayed in the proteins expression of ACE2, AT1R, and Ang (1-7) in vessel and kidney. More importantly, parental PM exposure further induced the increase in serous Ang II and the protein expression of AT1R in vessel, but decrease in ACE2 and Ang (1-7). The serous Ang II was positively associated with splenic T helper type 17 (Th17) cell population and serous IL (interleukin)-17A, but negatively associated with T regular (Treg) cell population and serous IL-10. The results suggested that parental air pollution exposure might induce the elevation of offspring blood pressure via mediate Th17- and Treg-related immune microenvironment.

Ambient fine particulate matter induced the elevation of blood pressure through ACE2/Ang(1-7) pathway: The evidence from urine metabolites.

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.

Fine particulate matter-induced cardiovascular injury is associated with NLRP3 inflammasome activation in Apo E-/- mice.

Epidemiological evidences have indicated that fine particulate matter (PM2.5) is associated with the increased risk of cardiovascular morbidity and mortality. Although several mechanisms linking PM2.5 and inflammatory responses have been widely implicated, the detailed mechanisms involving the occurrence of inflammation in PM2.5-induced adverse effects are lacking. This study aims to investigate whether PM2.5 exposure-induced cardiovascular injury is associated with NLRP3 inflammasome activation in apolipoprotein E-/- (Apo E-/-) mice. Thirty-two Apo E-/- mice were randomly divided into four groups. The mice were fed with normal chow (NC) or high-fat chow (HFC) for 10 weeks, respectively. From week 11, the mice were exposed to concentrated PM2.5 (PM) or filter air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. The cardiac function and myocardial injury were evaluated by echocardiography and histopathological examination. Meanwhile, the expression of NLRP3-related signaling pathway in myocardium was detected. Compared with the FA mice, the PM mice showed the underlying cardiac dysfunction and injury in both NC and HFC groups. Mononuclear macrophages (CD11c+) were significant higher in bone marrow of the PM mice than that in the FA mice, whilst CD206+ macrophages were lower. Accordingly, PM2.5 exposure induced the increase of circulating inflammatory cytokine TNF-α and decrease of anti-inflammatory cytokine IL-10. PM2.5 exposure was also associated with the activation of NLRP3 inflammasome, which characterized by elevated protein expression of NLRP3, ASC, caspase-1, IL-1ß and IL-18 in myocardium. All these results demonstrated PM2.5-related cardiac injury is mediated by macrophages polarization and NLRP3 inflammasome activation.

AMPK activation attenuates inflammatory response to reduce ambient PM2.5-induced metabolic disorders in healthy and diabetic mice.

Epidemiological and experimental studies have indicated that ambient fine particulate matter (PM2.5) exposure is associated with the occurrence and development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). However, the mechanism is not clear yet, and there are few studies to explore the possible prevention measure. In this study, C57BL/6 and db/db mice were exposed to concentrated PM2.5 or filtered air using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 12 weeks. From week 11, some of the mice were assigned to receive a subcutaneous injection of AMPK activator (AICAR). Lipid metabolism, glucose tolerance, insulin sensitivity and energy homeostasis were measured. Meanwhile, the respiratory, systemic and visceral fat inflammatory response was detected. The results showed that PM2.5 exposure induced the impairments of glucose tolerance, insulin resistance, lipid metabolism disorders and disturbances of energy metabolism in both C57BL/6 and db/db mice. These impairments might be consistent with the increased respiratory, circulating and visceral adipose tissue (VAT) inflammatory response, which was characterized by the release of IL-6 and TNF-α in lung, serum and VAT. More importantly, AICAR administration led to the significant enhancement of energy metabolism, elevation of AMPK as well as the decreased IL-6 and TNF-α in VAT of PM2.5-exposed mice, which suggesting that AMPK activation might attenuate the inflammatory responses in VAT via the inhibition of MAPKs and NFκB. The study indicated that exposure to ambient PM2.5 under the concentration which is often seen in some developing countries could induce the occurrence of metabolic disorders in normal healthy mice and exacerbate metabolic disorders in diabetic mice. The adverse impacts of PM2.5 on insulin sensitivity, energy homeostasis, lipid metabolism and inflammatory response were associated with AMPK inhibition. AMPK activation might inhibit PM2.5-induced metabolic disorders via inhibition of inflammatory cytokines release. These findings suggested that AMPK activation is a potential therapy to prevent some of the metabolic disorders attributable to air pollution exposure.

The essential function of CARD9 in diet-induced inflammation and metabolic disorders in mice.

Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)-treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9-/- and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected. The CARD9/MAPK pathway-related gene and protein were determined in insulin-responsive organs using Western blotting and quantitative PCR. The results showed that HFD-induced insulin resistance and impairment of glucose tolerance were more severe in WT mice than that in the CARD9-/- mice. CARD9 absence significantly modified O2 consumption, CO2 production and heat production. CARD9-/- mice displayed the lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both HFD- and ND-treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in WT mice but not in the CARD9-/- mice. The results indicated that CARD9 absence could be a vital protective factor in diet-induced obesity via the CARD9/MAPK pathway, which may provide new insights into the development of gene knockout to improving diet-induced obesity and metabolism disorder.

The severity of lung injury and metabolic disorders induced by ambient PM2.5 exposure is associated with cumulative dose.

Lots of epidemiological and experimental studies have found that ambient fine particulate matter (PM2.5) exposure is associated with the development of cardiopulmonary diseases, obesity and diabetes. This study focused on the effects of cumulative PM2.5 exposure on pulmonary and systemic inflammation and insulin resistance. Thirty-two 6-week-old male Balb/c mice were randomly divided into four groups (FA, PM, WEEK and DAY groups) and were continuously or intermittently exposed to concentrated PM2.5 or filtered air (FA) for four weeks using Shanghai Meteorological and Environmental Animal Exposure System ("Shanghai-METAS"). The levels of IL-6 and TNF-α in serum, bronchoalveolar lavage fluid (BALF), lung tissues and white adipose tissue (WAT) were measured. Meanwhile, the expression of NF-κB and phosphor-NF-κB in lung tissue was detected by Western blot. Glucose tolerance and insulin resistance were also determined at the end of exposure. The results found that the mice in PM group displayed moderate inflammatory cell infiltration in lung, whereas the mice in WEEK and DAY groups displayed slight inflammatory cell infiltration in lung. Compared with the mice in FA group, the mRNA expressions of IL-6 and TNF-α in lung tissue and WAT significantly increased in the mice of PM group. Importantly, IL-6 and TNF-α mRNA expressions in PM group were higher than those in WEEK and DAY groups. The protein expression of phospho-NF-κB in lung tissue showed that PM group showed the activation of NF-κB, which was higher than that in the WEEK and DAY groups. Meanwhile, the mice in PM group showed more severe glucose tolerance and insulin resistance than that in the WEEK and DAY groups. The results suggested that the reduction of PM2.5 cumulative exposure may alleviate pulmonary and adipose inflammation, insulin resistance and glucose tolerance impairment. The results provided a clue that the interruption of ambient PM2.5 exposures by systems such as indoor air purification could be of benefit to people's health.

[Intervention effects of selenium yeast on fine particulate matters-induced lung injury in rats].

OBJECTIVE: To evaluate if selenium yeast could inhibit the rat lung injury induced by ambient fine particulate matter( PM_(2. 5) ). METHODS: Fifty-six male SpragueDawley rats were randomly allocated in seven groups( n = 8 each). Saline control group, the rats were exposed to 0. 9% saline by instillation. PM_(2. 5) exposure group, rats were exposed to PM_(2. 5) by intra-tracheal instillation every other day for three times with the accumulated dose of 40 mg/kg. Selenium yeast treatment groups, three groups of rat were exposed to PM_(2. 5) . Then the rats were given low, middle and high dose of selenium yeast, and the doses were 8. 75, 17. 5 and 35 mg/kg, respectively. High dose selenium yeast control group, rats were given high dose of selenium yeast only. Solvent control group, therats were given 1% carboxymethyl cellulose. Saline and PM_(2. 5) were given in the first week. In the second week, selenium yeast and solvent were given by gavage. The rats were sacrificed 24 hours after the last gavage. The bronchoalveolar lavage fluid( BALF)was collected to count the neutrophils numbers and analyze the markers related to inflammation, oxidative stress and cell damage. The lung lobe that was not been lavaged was processed for light microscopic examination. RESULTS: The proportions of neutrophils in BALF and the pathologic scores of lung in PM_(2. 5) - exposed groups were significantly higher than control( P < 0. 05). Selenium yeast treatment caused decrease in tumor necrosis factor-α( TNF-α), interleukin-1ß( IL-1ß), lactate dehydrogenase( LDH), total protein( TP), alkaline phosphatase( AKP) and malondialdehyde( MDA) compared with the only PM_(2. 5) exposure group. Meanwhile, the dose-dependent increase in totalsuperoxide dismutase( T-SOD) and glutathione peroxidase( GSH-Px) activities were observed. There were no significant differences among the groups of saline control group, high dose selenium yeast control group and solvent control group. CONCLUSION: Selenium yeast treatment may protect against acute injury induced by PM_(2. 5) in rat lung.

[Effects of vitamin E and ω-3 fatty acids on protecting ambient PM_(2. 5)-induced cardiovascular injury].

OBJECTIVE: To observe whether vitamin E( Ve) and ω-3 polyunsaturated fatty acids( ω-3 FA) could prevent the fine particulate matter( PM_(2. 5))-induced cardiovascular injury and explore the potential mechanism. METHODS: The SD rats were assigned randomly to 8 groups, those were control group, PM_(2. 5)group, Ve treatment groups( 3, 10, 30 mg/( kg·d)) and ω-3 FA treatment groups( 10, 30 and 90 mg/( kg·d)). The rats were pretreated with different concentration of Ve and ω-3 FA separately for 14 days, then were exposed to ambient PM_(2. 5) by intratracheal instillation( 10 mg/kg BW). All the rats were sacrificed after the last PM_(2. 5) exposure, then the arterial blood, lungs and cardiac tissues were collected. The expressions of tumor necrosis factor-α( TNF-α), interleukin-1ß( IL-1ß), interleukin-6( IL-6) in serum, bronchoalveolar lavage fluid and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde( MDA), superoxide dismutase( SOD) and glutathione-peroxidase( GSH-Px) in serum and myocardium were also measured. RESULTS: Compared with the severe injury of rats in PM_(2. 5) exposure group, the rats in Ve or ω-3 FA groups had a slighter injury in lung and cardiac tissue with the increase of Ve and ω-3 FA. Similarly, the levels of IL-1ß, IL-6 in bronchoalveolar lavage fluid had a decreasing trend with the increase of Ve and ω-3 FA compared with the PM_(2. 5) exposure groups. Meanwhile, the expressions of TNF-α in Ve and ω-3 FA high dose groups were significantly reduced when compared with the PM_(2. 5) exposure group( P <0. 05). In addition, the MDA levels in serum were markedly decreased and the activities of SOD were significantly increased compared with the PM_(2. 5)exposure group( P < 0. 05 or P < 0. 01) whereas the SOD activities were elevated only in the ω-3 FA high dose groups( P < 0. 05). Meanwhile, the levels of IL-6 and TNF-α in serum had an obvious decrease compared with the PM_(2. 5) exposure group( P < 0. 01). Similarly, compared with the PM_(2. 5)exposure group, the expressions of MDA were markedly decreased and the activities of SOD and GSH-Px in myocardium were significantly increased( P < 0. 05 or P < 0. 01) in the Ve treatment group. In addition, the activities of GSH-Px was found higher only in the ω-3 FA high treatment group compared with the PM_(2. 5)exposure group( P < 0. 05). Meanwhile, the levels of IL-1ß and TNF-α in cardiac tissue had an obvious decrease trend with the increase of Ve and ω-3 FA. CONCLUSION: PM_(2. 5) exposure may increase inflammatory response and oxidative stress, supplementation with Ve and ω-3 FA could prevent the PM_(2. 5)-induced inflammatory reaction and oxidative stress damage by increasing the activities of SOD and GSH-Px.

Sex Differences in the Relationship Between Emotional Support and Self-rated Health among Chinese Elderly.

PURPOSE: This study aimed to explore sex differences in the association between emotional support and self-rated health among the elderly. DESIGN: This was a cross-sectional survey based on the sub-project of China's National Basic Public Health Service Project-Health Management Services for the Elderly. SETTING: Participants were recruited from ten rural townships in Jingyuan County, Gansu Province, Northwestern China. SUBJECTS: 1405 subjects aged 60 or above. METHODS: Emotional support (consisting of 5 items) and self-rated health (evaluated by EQ-VAS) were investigated in this study. Multiple linear regression was conducted to consider the potential relationship. RESULTS: The frequency of children visit and the number of providers of emotional support were positively associated with self-rated health among older women (ß = 1.13, 95%CI = 0.25-2.02; ß = 1.80, 95%CI = 1.01-2.58), whereas the number of close friends had a positive association with self-rated health among older men (ß = 1.11, 95%CI = 0.20-2.01). The number of close relatives and the frequency of seeking emotional support were not found to be associated with self-rated health among both older men and older women. CONCLUSION: The study has found that the relationship between emotional support and self-rated health was differed by sex, calling attention to the need for sex-specific interventions.

[Proportion and Clinical Significance of γδT17/Th17/Tc17 Cells in Peripheral Blood of Uygur Patients with Chronic Lymphoblastic Leukemia].

OBJECTIVE: To explore the distribution of γδT17/Th17/Tc17 cells in the peripheral blood of Uygur patients with chronic lymphoblastic leukemia (CLL) and clinical significance. METHODS: ELISA method was used to detect the levels of IL-17, IL-23, IL-6, and IFN-γ in the peripheral blood serum of 53 newly diagnosed Uygur patients with CLL and 30 healthy controls. Flow cytometry was used to determine the proportion of γδT/γδT17/Th17/Tc17 cells in the peripheral blood of Uygur CLL patients and controls, and the changes of the abover indexes in CLL Binet staging were observed. RESULTS: Compared with the control group, the proportion of γδT cells, γδT17 cells, and Th17 cells in the peripheral blood of Uygur CLL patients increased significantly （P <0.05）. γδT17 cell proportion in total lymphocytes was significantly higher than Th17 and Tc17 cell proportions（P <0.05）, and proportions of γδT, γδT17 cells increased gradually as the disease progressed. The levels of cytokines IL-17, IL-23, and IL-6 in peripheral blood of Uygur patients with CLL were significantly higher than those in the control group（P <0.05）, while the level of cytokine IFN-γ was significantly lower（P <0.05）. The level of IL-17 in peripheral blood decreased gradually as the disease progressed（P <0.05）. CONCLUSION: γδT and γδT17 are abnormally highly expressed in Uygur CLL , which are related to the stage of disease and participate in the occurrence and development of CLL.

Lifestyle deterioration linked to elevated inflammatory cytokines over a two-month follow-up.

Healthy lifestyle reduces the risk of inflammation-related diseases. This study assessed how lifestyle changes affect inflammatory cytokines over 2 months. Involving 179 apparently healthy participants recruited from community, collecting data on lifestyles (smoking, alcohol, BMI, daily activity, sleep, diet) and measured inflammatory cytokines (TNF-α, IL-1ß, IL-17A, CRP, IL-8, IL-18, IFN-γ) plus pepsinogens (PG I, PG II) at the baseline and 2-month follow-up. The combined adverse lifestyle score is the sum of scores across six lifestyles, with higher scores indicating more adverse lifestyle factors. Use multiple linear regression and mixed linear models to analyze the relationship between the changes in lifestyle and inflammatory cytokines (follow-up values minus baseline values). For every 1-point increase in combined adverse lifestyle score, IL-17A increased by 0.98 (95% CI 0.23, 1.73) pg/mL, IFN-γ increased by 1.79 (95% CI 0.39, 3.18) pg/mL. Decreased changes in daily activity were associated with higher IL-17A (ß = 1.83, 95% CI 0.53, 3.13) and IFN-γ (ß = 2.59, 95% CI 0.9, 4.98). Excluding daily activity, changes in combined adverse lifestyle scores were not associated with changes in inflammatory cytokines. Lifestyle improvements at 2-month intervals may reduce TNF-α, IL-17A and IFN-γ, with daily activity making the greatest contribution.

Light-driven micro/nanomotors in biomedical applications.

Nanotechnology brings hope for targeted drug delivery. However, most current drug delivery systems use passive delivery strategies with limited therapeutic efficiency. Over the past two decades, research on micro/nanomotors (MNMs) has flourished in the biomedical field. Compared with other driven methods, light-driven MNMs have the advantages of being reversible, simple to control, clean, and efficient. Under light irradiation, the MNMs can overcome several barriers in the body and show great potential in the treatment of various diseases, such as tumors, and gastrointestinal, cardiovascular and cerebrovascular diseases. Herein, the classification and mechanism of light-driven MNMs are introduced briefly. Subsequently, the applications of light-driven MNMs in overcoming physiological and pathological barriers in the past five years are highlighted. Finally, the future prospects and challenges of light-driven MNMs are discussed as well. This review will provide inspiration and direction for light-driven MNMs to overcome biological barriers in vivo and promote the clinical application of light-driven MNMs in the biomedical field.

The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Dyslipidemia, a condition implying high cardiovascular risks, has been widely studied on its potential nutrition interventions, including functional foods. This study aims to examine the effect of nattokinase monascus supplements (NMSs) on cardiovascular biomarkers and carotid intima-media thickness (CIMT) in patients with dyslipidemia. A total of 113 eligible subjects were randomly assigned to receive either NMSs or a placebo (55 and 58, respectively). After a 120-day intervention, there were significant mean absolute changes in total cholesterol (TC), low-density cholesterol (LDL-C), non-high-density cholesterol (non-HDL-C), and low-density cholesterol to high-density cholesterol ratio (LDL-C to HDL-C ratio), with values of -0.52 (95% CI: -0.51 to -0.54) mmol/L, -0.43 (95% CI: -0.45 to -0.41) mmol/L, -0.52 (95% CI: -0.52 to -0.52) mmol/L, and -0.29 (95% CI: -0.30 to -0.28) mmol/L, respectively, between the two groups. However, no significant differences were found in triglycerides (TGs), high-density cholesterol (HDL-C), and CIMT. Furthermore, the results for lipids and CIMT remained essentially unchanged after adjusting for various confounding factors using the analysis of covariance model. There were no significant differences in coagulation, liver function, renal function, or other indicators. No intervention-related adverse events, such as mouth ulcers, drooling, and stomach pain, were reported. The study results demonstrate that NMSs can ameliorate lipid levels (TC, LDL-C, non-HDL-C, and the LDL-C to HDL-C ratio) without the occurrence of adverse events. However, it did not significantly affect serum TG, HDL-C, and CIMT.

Galectin-9 and myeloid-derived suppressor cell as prognostic indicators for chronic lymphocytic leukemia.

BACKGROUND: Galectin-9 and myeloid-derived suppressor cells (MDSCs) have an important role in tumors, but their clinical values in chronic lymphocytic leukemia (CLL) have not been fully elucidated. This study aimed to analyze the prognosis values of Galectin-9 and MDSCs in CLL. METHODS: The concentrations of Galectin-9, argininase-1, and inducible nitric oxide synthase in serum were detected by enzyme-linked immune sorbent assay. The expression of Tim-3 protein in peripheral blood mononuclear cell was detected by Western blot. Flow cytometry was used to analyze the percentages of Tim-3 on T-cells (CD3+ T, CD4+ T, and CD8+ T cells) and MDSCs. RESULTS: Our results showed that Galectin-9 and MDSCs significantly increased in CLL patients and were closely related to the disease progression. Patient's receiver operating characteristic, progression-free survival, and Cox regression analysis showed that Galectin9 and MDSCs were poor prognostic factors of CLL. CONCLUSION: Galectin-9 and MDSCs were associated with clinical progression and could be important prognostic indicators for CLL.

Recent progress of micro/nanomotors to overcome physiological barriers in the gastrointestinal tract.

Oral administration is a convenient administration route for gastrointestinal disease therapy with good patient compliance. But the nonspecific distribution of the oral drugs may cause serious side effects. In recent years, oral drug delivery systems (ODDS) have been applied to deliver the drugs to the gastrointestinal disease sites with decreased side effects. However, the delivery efficiency of ODDS is tremendously limited by physiological barriers in the gastrointestinal sites, such as the long and complex gastrointestinal tract, mucus layer, and epithelial barrier. Micro/nanomotors (MNMs) are micro/nanoscale devices that transfer various energy sources into autonomous motion. The outstanding motion characteristics of MNMs inspired the development of targeted drug delivery, especially the oral drug delivery. However, a comprehensive review of oral MNMs for the gastrointestinal diseases therapy is still lacking. Herein, the physiological barriers of ODDS were comprehensively reviewed. Afterward, the applications of MNMs in ODDS for overcoming the physiological barriers in the past 5 years were highlighted. Finally, future perspectives and challenges of MNMs in ODDS are discussed as well. This review will provide inspiration and direction of MNMs for the therapy of gastrointestinal diseases, pushing forward the clinical application of MNMs in oral drug delivery.

High leukocyte-to-lymphocyte ratio is associated with acute relapse in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated chronic disease characterized by inflammatory demyelination in the central nervous system (CNS).As there is limited evidence on whether leukocyte-to-lymphocyte ratios (LLRs) are associated with MS, we carried out an investigation on the association between LLRs and MS as favorable markers and aimed to determine the cut-off LLR for the identification of early-stage MS patients. METHODS: A matched case-control study enrolled a total of 120 MS inpatients and 120 age- and sex-matched non-MS inpatients from January 2013 to June 2018. LLRs were tested from peripheral venous blood routinely during hospitalization. Conditional logistic regression analyses were used to explore differences in LLRs between cases and controls. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic ability of LLRs and determine the best cut-off value. Disease disability was assessed using the Expanded Disability Status Scale (EDSS). RESULTS: The LLR was significantly associated with MS in hospitalized patients (OR: 2.372, 95% CI: 1.282 to 4.387, p < 0.001) after adjusting for potential confounders. The area under the curve (AUC) value was 0.793 (95% CI: 0.736 to 0.851). The cut-off value for LLR was 3.18, with sensitivity and specificity values of 62.5% (95% CI: 53.2% to 71.2%) and 88.3% (95% CI: 81.2% to 93.5%), respectively. The EDSS scores of the higher LLR group were significantly higher than the lower group. CONCLUSION: Systemic inflammation measured using LLRs may be an inflammatory marker among MS inpatients. LLRs may serve as favorable inflammatory markers with which to discriminate MS among Chinese subjects.

Ambient PM2.5-induced brain injury is associated with the activation of PI3K/AKT/FoxO1 pathway.

PM2.5-related neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. Six-week-old male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM2.5 or filtered air for 2, 4, and 6 months, respectively. The neurobehavioral changes of mice were tested. The weight of the whole brain and olfactory bulbs were recorded at the end of exposure, and the brain structure was observed by hematoxylin and eosin (HE) staining. Serum indicators, mRNA, and protein expressions were detected. The spatial learning memory ability was impaired, and the mice were more anxious after PM2.5 exposure. Relative brain weight decreased with age, and PM2.5 exposure exceeded the decrease of relative brain weight. Interestingly, superoxide dismutase (SOD) and albumin decreased in the PM2.5-exposed groups although neuronal morphology and other serum indicators did not show significant difference between PM and FA groups. Moreover, PM2.5 induced the increase of plasminogen at 2 months but recovered at 4 months and then increased at 6 months again. The results from protein expression and transcriptomic test demonstrated that PI3K/AKT/FoxO1 pathway might be activated after 6-month PM2.5 exposure in mice. Indicators albumin, the percentage of albumin over IgG (A/G value), and plasminogen were the main serous changes in mice after early-stage (2 months) and long-term (6 months) PM2.5 exposure. In addition, early-stage injury induced by PM2.5 might recover at later time point and display significant injury again with the exposure time. PM2.5 exposure-induced brain injury might be associated with the activation of PI3K/AKT/FoxO1 pathway.