Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.     

Hygiene Behaviors Associated with Influenza-Like Illness among Adults in Beijing,China: A Large,Population-Based Survey

The objective of this study was to identify possible hygiene behaviors associated with the incidence of ILI among adults in Beijing. In January 2011, we conducted a multi-stage sampling, cross-sectional survey of adults living in Beijing using self-administered anonymous questionnaires. The main outcome variable was self-reported ILI within the past year. Multivariate logistic regression was used to identify factors associated with self-reported ILI. A total of 13003 participants completed the questionnaires. 6068 (46.7%) of all participants reported ILI during the past year. After adjusting for demographic characteristics, the variables significantly associated with a lower likelihood of reporting ILI were regular physical exercise (OR 0.80; 95% CI 0.74–0.87), optimal hand hygiene (OR 0.87; 95% CI 0.80–0.94), face mask use when going to hospitals (OR 0.87; 95% CI 0.80–0.95), and not sharing of towels and handkerchiefs (OR 0.68; 95% CI 0.63–0.73). These results highlight that personal hygiene behaviors were potential preventive factors against the incidence of ILI among adults in Beijing, and future interventions to improve personal hygiene behaviors are needed in Beijing.     

Pattern Selection in Network of Coupled Multi-Scroll Attractors

Multi-scroll chaotic attractor makes the oscillator become more complex in dynamic behaviors. The collective behaviors of coupled oscillators with multi-scroll attractors are investigated in the regular network in two-dimensional array, which the local kinetics is described by an improved Chua circuit. A feasible scheme of negative feedback with diversity is imposed on the network to stabilize the spatial patterns. Firstly, the Chua circuit is improved by replacing the nonlinear term with Sine function to generate infinite aquariums so that multi-scroll chaotic attractors could be generated under appropriate parameters, which could be detected by calculating the Lyapunov exponent in the parameter region. Furthermore, negative feedback with different gains (D₁, D₂) is imposed on the local square center area A₂ and outer area A₁ of the network, it is found that spiral wave, target wave could be developed in the network under appropriate feedback gain with diversity and size of controlled area. Particularly, homogeneous state could be reached after synchronization by selecting appropriate feedback gain and controlled size in the network. Finally, the distribution for statistical factors of synchronization is calculated in the two-parameter space to understand the transition of pattern region. It is found that developed spiral waves, target waves often are associated with smaller factor of synchronization. These results show that emergence of sustained spiral wave and continuous target wave could be effective for further suppression of spatiotemporal chaos in network by generating stable pacemaker completely.     

Staphylococcus aureus Sortase A-Mediated Incorporation of Peptides: Effect of Peptide Modification on Incorporation

The endogenous Staphylococcus aureus sortase A (SrtA) transpeptidase covalently anchors cell wall-anchored (CWA) proteins equipped with a specific recognition motif (LPXTG) into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG motif (K(FITC)LPETG-amide) into the bacterial cell wall, albeit at high concentrations of 500 μM to 1 mM. In the present study, we have evaluated the effect of substrate modification on the incorporation efficiency. This revealed that (i) by elongation of LPETG-amide with a sequence of positively charged amino acids, derived from the C-terminal domain of physiological SrtA substrates, the incorporation efficiency was increased by 20-fold at 10 μM, 100 μM and 250 μM; (ii) Substituting aspartic acid (E) for methionine increased the incorporation of the resulting K(FITC)LPMTG-amide approximately three times at all concentrations tested; (iii) conjugation of the lipid II binding antibiotic vancomycin to K(FITC)LPMTG-amide resulted in the same incorporation levels as K(FITC)LPETG-amide, but much more efficient at an impressive 500-fold lower substrate concentration. These newly developed synthetic substrates can potentially find broad applications in for example the in situ imaging of bacteria; the incorporation of antibody recruiting moieties; the targeted delivery and covalent incorporation of antimicrobial compounds into the bacterial cell wall.     

The Prognostic Value of Peak Cardiac Power Output in Chinese Patients with Chronic Heart Failure

Background

Cardiopulmonary exercise testing has been widely used to risk stratify patients with chronic heart failure (CHF). Peak oxygen consumption (peakVO₂) was regarded as a powerful predictor of survival, as it is a surrogate for peak cardiac output (CO), which by most is considered the “true” measure of heart failure. Therefore, it is reasonable to hypothesize that CO is an even stronger predictor than peak VO₂. The present study is aimed to investigate the prognostic value of peak cardiac power output (peak CPO) in comparison with peakVO₂ in Chinese patients with CHF.

Methods

Participants provided written informed consent to participate in this study. Totally 129 patients with CHF underwent symptom-limited cardiopulmonary exercise testing (CPET), with mean age 59.1±11.4 years, 87.6% male, 57.4% ischemic etiology, body mass index (BMI) 24.7±3.7 kg/m² and LVEF 38±9%. CO was measured using an inert gas rebreathing method. The primary endpoints are cardiac deaths.

Results

Over median 33.7-month follow-up, 19 cardiac deaths were reported. Among peak VO₂,VE/VCO₂ slope and Peak CPO, their area under ROC were 0.64, 0.67, 0.68, respectively (Ρ<0.05).The optimal thresholds for predicting cardiac deaths were peak VO₂≤13.4 ml.kg^-1.min^-1, and VE/VCO₂ slope≥39.3 and peak CPO≤ 1.1 respectively by ROC analysis. Finally, in patients with a peak VO2≤13.4 ml.kg^-1.min^-1 those with peak CPO>1.1W had better survival than those with peak CPO ≤ 1.1W. However, by multivariate analysis adjusted for age, sex, BMI, resting heart rate, LVMI, LVEF, Peak CPO was not an independent predictor of cardiac deaths (P> 0.05).

Conclusions

Peak CPO was not a predictor of cardiac death in Chinese CHF patients.     

Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes

The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D) pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs) from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.     

Analysis of Plasma Cytokine and Chemokine Profiles in Patients with and without Tuberculosis by Liquid Array-Based Multiplexed Immunoassays

The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guérin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-α, IL-6, IP-10, IFN-γ, and MIP-1β were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-α plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-γ, and MIP-1β were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1β was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-α may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-γ) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics.     

Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide,Cross-Sectional 3B Study

Background

There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients.

Methods

Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24–27.9kg/m² and ≥28.0kg/m². Central obesity was defined as a waist circumference ≥80cm in women and ≥85cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90mmHg and LDL-C<2.6mmol/L.

Results

Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals.

Conclusions

Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.     

Serum TGF-β1 as a Biomarker for Type 2 Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials

Background

Abnormal expression of serum TGF-β1 was found in patients with diabetic nephropathy. However, the association of TGF-β1 with the risk of diabetic nephropathy remains unknown. The present study was undertaken to investigate whether such an association exists.

Methods

We searched the Chinese VIP, Wangfang, China National Knowledge Infrastructure, PubMed, Embase, and Google Scholar databases for relevant studies and extracted all eligible data. Stata12 software was used for statistical analysis.

Results

Nine reports met our criteria and were used for data extraction. There were 264 patients and 227 healthy controls from qualified reports in this meta-analysis. The results suggested that serum TGF-β1 levels were significantly up-regulated in patients with diabetic nephropathy; the instrumental variable was 3.94 (95% confidence interval 3.20–4.68, p<0.01).

Conclusions

Meta-analysis suggested that elevated serum TGF-β level in patients with diabetes is associated with a high risk of nephropathy. Further studies are required to validate these observations.