Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection.

Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease.

Transforming Spirulina maxima Biomass into Ultrathin Bioactive Coatings Using an Atmospheric Plasma Jet: A New Approach to Healing of Infected Wounds.

The challenge of wound healing, particularly in patients with comorbidities such as diabetes, is intensified by wound infection and the accelerating problem of bacterial resistance to current remedies such as antibiotics and silver. One promising approach harnesses the bioactive and antibacterial compound C-phycocyanin from the microalga Spirulina maxima. However, the current processes of extracting this compound and developing coatings are unsustainable and difficult to achieve. To circumvent these obstacles, a novel, sustainable argon atmospheric plasma jet (Ar-APJ) technology that transforms S. maxima biomass into bioactive coatings is presented. This Ar-APJ can selectively disrupt the cell walls of S. maxima, converting them into bioactive ultrathin coatings, which are found to be durable under aqueous conditions. The findings demonstrate that Ar-APJ-transformed bioactive coatings show better antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, these coatings exhibit compatibility with macrophages, induce an anti-inflammatory response by reducing interleukin 6 production, and promote cell migration in keratinocytes. This study offers an innovative, single-step, sustainable technology for transforming microalgae into bioactive coatings. The approach reported here has immense potential for the generation of bioactive coatings for combating wound infections and may offer a significant advance in wound care research and application.

High Solubility and Bioavailability of Lobster Shell-Derived Calcium for Significantly Proliferating Bone and Skin Cells In Vitro.

Shell wastes pose environmental and financial burdens to the shellfish industry. Utilizing these undervalued shells for commercial chitin production could minimize their adverse impacts while maximizing economic value. Shell chitin conventionally produced through harsh chemical processes is environmentally unfriendly and infeasible for recovering compatible proteins and minerals for value-added products. However, we recently developed a microwave-intensified biorefinery that efficiently produced chitin, proteins/peptides, and minerals from lobster shells. Lobster minerals have a calcium-rich composition and biologically originated calcium is more biofunctional for use as a functional, dietary, or nutraceutical ingredient in many commercial products. This has suggested a further investigation of lobster minerals for commercial applications. In this study, the nutritional attributes, functional properties, nutraceutical effects, and cytotoxicity of lobster minerals were analyzed using in vitro simulated gastrointestinal digestion combined with growing bone (MG-63), skin (HaCaT), and macrophage (THP-1) cells. The calcium from the lobster minerals was found to be comparable to that of a commercial calcium supplement (CCS, 139 vs. 148 mg/g). In addition, beef incorporated with lobster minerals (2%, w/w) retained water better than that of casein and commercial calcium lactate (CCL, 21.1 vs. 15.1 and 13.3%), and the lobster mineral had a considerably higher oil binding capacity than its rivals (casein and CCL, 2.5 vs. 1.5 and 1.0 mL/g). Notably, the lobster mineral and its calcium were far more soluble than the CCS (98.4 vs. 18.6% for the products and 64.0 vs. 8.5% for their calcium) while the in vitro bioavailability of lobster calcium was 5.9-fold higher compared to that of the commercial product (11.95 vs. 1.99%). Furthermore, supplementing lobster minerals in media at ratios of 15%, 25%, and 35% (v/v) when growing cells did not induce any detectable changes in cell morphology and apoptosis. However, it had significant effects on cell growth and proliferation. The responses of cells after three days of culture supplemented with the lobster minerals, compared to the CCS supplementation, were significantly better with the bone cells (MG-63) and competitively quick with the skin cells (HaCaT). The cell growth reached 49.9-61.6% for the MG-63 and 42.9-53.4% for the HaCaT. Furthermore, the MG-63 and HaCaT cells proliferated considerably after seven days of incubation, reaching 100.3% for MG-63 and 115.9% for HaCaT with a lobster mineral supplementation of 15%. Macrophages (THP-1 cells) treated for 24 h with lobster minerals at concentrations of 1.24-2.89 mg/mL had no detectable changes in cell morphology while their viability was over 82.2%, far above the cytotoxicity threshold (<70%). All these results indicate that lobster minerals could be used as a source of functional or nutraceutical calcium for commercial products.

Refractory neutrophilic asthma and ciliary genes.

BACKGROUND: Refractory asthma (RA) remains poorly controlled, resulting in high health care utilization despite guideline-based therapies. Patients with RA manifest higher neutrophilia as a result of increased airway inflammation and subclinical infection, the underlying mechanisms of which remain unclear. OBJECTIVE: We sought to characterize and clinically correlate gene expression differences between refractory and nonrefractory (NR) asthma to uncover molecular mechanisms driving group distinctions. METHODS: Microarray gene expression of paired airway epithelial brush and endobronchial biopsy samples was compared between 60 RA and 30 NR subjects. Subjects were hierarchically clustered to identify subgroups of RA, and biochemical and clinical traits (airway inflammatory molecules, respiratory pathogens, chest imaging) were compared between groups. Weighted gene correlation network analysis was used to identify coexpressed gene modules. Module expression scores were compared between groups using linear regression, controlling for age, sex, and body mass index. RESULTS: Differential gene expression analysis showed upregulation of proneutrophilic and downregulation of ciliary function genes/pathways in RA compared to NR. A subgroup of RA with downregulated ciliary gene expression had increased levels of subclinical infections, airway neutrophilia, and eosinophilia as well as higher chest imaging mucus burden compared to other RA, the dominant differences between RA and NR. Weighted gene correlation network analysis identified gene modules related to ciliary function, which were downregulated in RA and were associated with lower pulmonary function and higher airway wall thickness/inflammation, markers of poorer asthma control. CONCLUSIONS: Identification of a novel ciliary-deficient subgroup of RA suggests that diminished mucociliary clearance may underlie repeated asthma exacerbations despite adequate treatment, necessitating further exploration of function, mechanism, and therapeutics.

Baseline type 2 biomarker levels and response to tezepelumab in severe asthma.

BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER. METHODS: Adults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)-5, IL-13, periostin, thymus and activation-regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels. RESULTS: Positive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL-5, IL-13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55-83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL-5, IL-13, periostin, TARC, or TSLP, when these biomarkers were assessed individually. CONCLUSION: At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.

The relationship between airway immunoglobulin activity and eosinophils in COPD.

In chronic obstructive pulmonary disease (COPD), the effects of inhaled corticosteroids are predicted by blood eosinophil counts. We previously briefly reported increased immunoglobulin (Ig)A and IgM levels in bronchoalveolar lavage (BAL) of COPD patients with higher (eosinophilhigh ) compared to lower (eosinophillow ) blood eosinophils (>250/µL versus < 150/µL), suggesting differences in adaptive immune function. An inverse relationship exists between eosinophil counts and airway pathogenic bacteria levels. The mechanistic reasons for these associations between eosinophils, corticosteroids and pathogenic bacteria are unclear. IgA, IgM and IgG levels were assessed in BAL, bronchial biopsies and epithelium collected from eosinophilhigh (n = 20) and eosinophillow (n = 21) patients. Bronchial B-cell numbers were measured by immunohistochemistry. B-cell activity was assessed in bronchial samples and following exposure to BAL from eosinophilhigh and eosinophillow patients. BAL levels of non-typeable Haemophilus influenza (NTHi)-specific immunoglobulins were quantified. Results showed airway expression of IgA, IgG1 and IgM were lower in eosinophillow compared to eosinophilhigh patients, with lower levels of NTHi-specific IgA and IgM. Bronchial B-cell numbers were similar in both groups, but B-cell activity was lower in eosinophillow patients. In conclusion, COPD eosinophillow patients show differences in adaptive immune function compared to COPD eosinophilhigh patients. These differences may cause different microbiomes in these COPD phenotypes.

Insight into the Influence of Analyte Molecular Structure Targeted on MoS2-GO-Coated Electrochemical Nanosensors.

MoS2-GO composites were fabricated by an ultrasonication method at room temperature. Raman spectra, emission scanning electron microscopy (SEM), and transmission electron microscopy (TEM) images were used to study the structural characteristics, morphologies, and sizes of the synthesized materials. An MoS2-GO/SPE (screen-printed electrode) was prepared by a facile dropping method and acted as an effective electrochemical sensor toward clenbuterol (CLB) and 4-nitrophenol (4-NP) detection. Based on the obtained results, the influence of analyte molecular structure on the adsorption ability and electronic interoperability between the targeted analyte and electrode surface were investigated in detail and discussed as well, through some electrochemical kinetic parameters (electron/proton-transfer number, electron transfer rate constant (ks), charge transfer coefficient, and adsorption capacity (Γ)). In particular, it should be stressed that 4-NP molecules possess a simple molecular structure with many positive effects (electronic, conjugation, and small steric effects) and flexible functional groups, resulting in fast electron transport/charge diffusion and effective adsorption process as well as strong interactions with the electrode surface. Therefore, 4-NP molecules have been facilitated better in electrochemical reactions at the electrode surface and electrode-electrolyte interfaces, leading to improved current response and electrochemical sensing performance, compared with those of CLB.

Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases.

BACKGROUND: Benralizumab, a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor α, depletes eosinophils and basophils by enhanced antibody-dependent cell-mediated cytotoxicity. It demonstrated efficacy for patients with moderate to severe asthma and, in a Phase IIa trial, for chronic obstructive pulmonary disease (COPD) with eosinophilic inflammation. We investigated effects of benralizumab 100 mg every 8 weeks (first three doses every 4 weeks) subcutaneous on blood inflammatory markers through proteomic and gene-expression analyses collected during two Phase II studies of patients with eosinophilic asthma and eosinophilic COPD. METHODS: Serum samples for proteomic analysis and whole blood for gene expression analysis were collected at baseline and 52 weeks (asthma study) or 32 weeks (COPD study) post-treatment. Proteomic analyses were conducted on a custom set of 90 and 147 Rules-Based Medicine analytes for asthma and COPD, respectively. Gene expression was profiled by Affymetrix Human Genome U133 plus 2 arrays (~ 54 K probes). Gene set variation analysis (GSVA) was used to determine transcriptomic activity of immune signatures. Treatment-related differences between analytes, genes, and gene signatures were analyzed for the overall population and for patient subgroups stratified by baseline blood eosinophil count (eosinophil-high [≥300 cells/µL] and eosinophil-low [< 300 cells/µL]) via t-test and repeated measures analysis of variance. RESULTS: Eosinophil chemokines eotaxin-1 and eotaxin-2 were significantly upregulated (false discovery rate [FDR] < 0.05) by approximately 2.1- and 1.4-fold in the asthma study and by 2.3- and 1.7-fold in the COPD study following benralizumab treatment. Magnitude of upregulation of these two chemokines was greater for eosinophil-high patients than eosinophil-low patients in both studies. Benralizumab was associated with significant reductions (FDR < 0.05) in expression of genes associated with eosinophils and basophils, such as CLC, IL-5Rα, and PRSS33; immune-signaling complex genes (FCER1A); G-protein-coupled receptor genes (HRH4, ADORA3, P2RY14); and further immune-related genes (ALOX15 and OLIG2). The magnitude of downregulation of gene expression was greater for eosinophil-high than eosinophil-low patients. GSVA on immune signatures indicated significant treatment reductions (FDR < 0.05) in eosinophil-associated signatures. CONCLUSIONS: Benralizumab is highly selective, modulating blood proteins or genes associated with eosinophils or basophils. Modulated protein and gene expression patterns are most prominently altered in eosinophil-high vs. eosinophil-low patients. TRIAL REGISTRATION: NCT01227278 and NCT01238861 .

One-Pot Synthesis of Magnesium Aminoclay-Iron Oxide Nanocomposites for Improved Photo-Fenton Catalytic Performance.

Fe3O4 nanoparticles (NPs) have been widely used in photo-Fenton catalysis applications for water/waste water treatment. Their drawbacks, however, continue to limit their potential. In the present study, we synthesized magnesium aminoclay-iron oxide [MgAC-Fe3O4] nanocomposites in DI water solution by treated them under 4% H2/Ar for 3 hours in a 500 °C furnace. Obtained X-ray diffraction (XRD) patterns confirmed that the growth of the Fe3O4 NPs in the amorphous MgAC; also, scanning electron microscopy (SEM) images indicated that the MgAC-Fe3O4 nanocomposites were in an aggregated form of 170±117 nm average-diameter. MgAC[0.7 g]-Fe3O4 nanocomposite exhibited the best photo-Fenton catalysis with methylene blue (MB) was completely removed from the treatment solution at a constant rate of 0.0083 (min-1) on the batch scale. This performance was 13.83 times better than that of commercial Fe3O4. On the pilot scale (100 L), MgAC[0.7 g]- Fe3O4 nanocomposite took 12 hours to completely removed MB from tap water. The mechanism of the high photo-Fenton catalysis was attributed to the higher rate adsorption of MgAC as well as Brunauer-Emmett-Teller (BET) surface area.

Airway and serum biochemical correlates of refractory neutrophilic asthma.

BACKGROUND: Despite progress in the diagnosis and management of asthma, many patients have poorly controlled or refractory asthma (RA). The mechanism of this RA is not well understood. OBJECTIVE: We sought to explore the relationship between neutrophils and other biomarkers of RA. METHOD: Sixty patients with RA, 30 patients with nonrefractory asthma (NRA), and 20 healthy subjects were enrolled. We performed a comprehensive characterization of these study subjects, which included laboratory and pulmonary function studies, chest computed tomography, and bronchoscopy with bronchoalveolar lavage (BAL). We analyzed BAL fluid and serum for a total of 244 biomolecules using a multiplex assay and correlated them with clinical and other laboratory parameters. RESULTS: RA was significantly different from NRA with regard to pulmonary function indices, bronchial basement membrane thickness, and BAL fluid neutrophil and lymphocyte counts but not eosinophil counts. BAL fluid neutrophil counts negatively and positively correlated with forced vital capacity and age, respectively. Of the 244 biomolecules studied, 52 and 14 biomolecules from BAL fluid and serum, respectively, were significantly different among the study groups. Thirteen of these 52 molecules correlated with BAL fluid neutrophil counts. BAL fluid from 40% of patients with RA was positive for a pathogenic microbe. Infection-negative neutrophilic RA was associated with an increase in levels of select biomarkers of inflammation in the serum, suggesting the presence of systemic inflammation. CONCLUSIONS: RA was associated with increased numbers of neutrophils and proneutrophilic biomolecules in the airways. Subclinical infection was present in 40% of patients with RA, which likely contributed to neutrophilic inflammation. A subgroup of patients with noninfected neutrophilic RA was associated with systemic inflammation.

A Sputum Proteomic Signature That Associates with Increased IL-1ß Levels and Bacterial Exacerbations of COPD.

PURPOSE: Activation of the interleukin-1ß (IL-1ß) signaling pathway has been implicated in COPD, but the proportion of COPD subjects whose disease is principally driven by activation of this pathway is poorly understood. In this study, we sought to differentiate an IL-1ß-associated sputum signature from other inflammation-associated COPD phenotypes. METHODS: Luminex-multiplex assays were used to study IL-1ß-mediated signature proteins within airway epithelium, smooth muscle, and vascular endothelial cell cultures. The IL-1ß-mediated signature was tested in a longitudinal study comprising of 35 paired stable-COPD and acute exacerbation (AECOPD) sputum samples. The presence of respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae, and P. aeruginosa) was evaluated by sputum cultures. RESULTS: Five proteins namely TNF-α, GCSF, IL-6, CD-40L, and MIP-1ß were found to be IL-1ß-regulated across all donors and cell types. All five of these IL-1ß-mediated proteins were significantly increased (p < 0.05) in sputum corresponding to AECOPD events showing at least a twofold increase in IL-1ß (IL-1ß(+) events, 18 of 35 total events), relative to preceding stable-COPD state. Sputum IL-1ß levels showed no significant association (p > 0.05, spearman) with known markers of other major COPD inflammation phenotypes. In addition, there was a significant association with bacterial presence in sputum culture with an odds ratio of 9 (95 % CI 1.56, 51.9) in IL-1ß(+) events versus IL-1ß(-) events. CONCLUSION: Our findings provide insights into potential markers of IL-1ß-associated AECOPD, and reaffirm association between IL-1ß pathway activation and airway bacterial infection in COPD. Taken together, our findings could help identify COPD patient subsets who may benefit from therapies targeting IL-1ß pathway.

Enhancing Nutritional Status and Addressing Micronutrient Deficiencies: Evaluating the Impact of Workplace Nutrition Program on Female Workers in Vietnam.

This randomized controlled clinical study aimed to assess the effectiveness of a nutrition intervention program for non-pregnant female workers in Vietnam. A total of 500 female workers were randomly assigned to the intervention and control groups. Participants in the intervention group were provided nutrition education, personalized specific dietary, and received oral nutrition supplements (ONS)-which contained multi-minerals and vitamins according to recommendations for adults for a duration of 12 wk, while participants in the control group received only nutrition education. The result shows the percentage of malnutrition by BMI in the control group rose from 15.6% to 21.3% after 12 wk; the figure for counterpart experienced a remain unchanged (p<0.05). Additionally, the mean of serum zinc in the intervention group significantly increased from 49.0±21.2 µg/dL to 53.6±19.5 µg/dL after 12 wk. Moreover, the intervention group demonstrated significant increases in serum iron and total serum calcium levels (p<0.05), with from 13.9±5.6 µmol/L to 15.3±5.8 µmol/L, and from 2.36±0.15 mmol/L to 2.4±0.09 mmol/L, respectively. The participants of the intervention group were more likely to have higher total serum calcium (Coef=0.04, p<0.05), serum iron (Coef=1.99, p<0.05), and serum zinc (Coef=18.9, p<0.05), which presents a reduce micronutrient deficiency. In conclusion, workplace nutrition interventions effectively mitigate micronutrient deficiencies and improve the nutritional status of female workers.

Treating moderate-to-severe atopic dermatitis with benralizumab: results from the HILLIER study, a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Atopic dermatitis (AD) is a chronic (long-lasting) skin disease that leads to dry, itchy, and swollen red spots, which can also be painful and flare up at any time. Some people with AD have a high number of eosinophils, a type of white blood cell, which are associated with worse disease. Medicated creams and lotions, prescribed by health care providers, are meant to reduce the symptoms of AD. For some people, these creams and lotions do not work. Benralizumab injection is a medication that reduces and removes eosinophils. A clinical trial called HILLER tested benralizumab to see if there was a difference in symptoms of AD after reducing or removing eosinophils. This article explains how benralizumab reduced eosinophils and the effect it had on AD symptoms in the HILLIER study. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Benralizumab reduced blood eosinophil numbers. However, benralizumab showed no evidence of treatment benefit on signs, symptoms, or severity of AD, as measured by three skin assessments compared with placebo. Benralizumab was well tolerated and had a safety profile that was consistent with previous studies. The five most commonly reported side effects were COVID-19 infection, upper respiratory tract infection, headache, swelling of the lymph nodes, and pink eye (conjunctivitis) in patients who received either benralizumab or placebo. WHAT ARE THE KEY TAKEAWAYS?: Benralizumab lowered the number of blood eosinophils without improving AD symptoms and was well tolerated.

CD40 ligand antagonist dazodalibep in Sjögren's disease: a randomized, double-blinded, placebo-controlled, phase 2 trial.

Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren's syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, -6.3 ± 0.6; PBO, -4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, -1.8 ± 0.2; PBO, -0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 .

Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus.

BACKGROUND: Circulating plasmablasts/plasma cells and activated B and T cells are increased in systemic lupus erythematosus (SLE). Interleukin (IL)-6 induces differentiation of B cells into antibody-forming cells and of T cells into effector cells. OBJECTIVE: To examine the hypothesis that blocking IL-6 would reverse some of the immune abnormalities present in SLE. METHODS: Fifteen patients with SLE with mild-to moderate disease activity were treated with biweekly infusions of tocilizumab, a humanised anti-IL-6 receptor monoclonal antibody for 12 weeks. Lymphocyte subsets (analysed by flow cytometry) and serum immunoglobulin levels were compared at baseline and at weeks 6 and 12. RESULTS: Tocilizumab decreased activated T and B cells, the frequency of CD27(high)CD38(high)IgD- plasmablasts/plasma cells and IgD-CD27+ post-switched memory B cells as well as IgG+ memory B cell, whereas it increased the frequency of IgD+CD27- antigen-inexperienced B cells. Among antigen-inexperienced IgD+CD27- B cells, CD38(low) mature naïve B cells increased significantly and CD38(Intermediate)CD5+ pre-naïve B cells showed a decreasing trend, whereas CD38(high)CD5+ transitional type 1 B cells did not change. Most of the changes occurred in patients who had abnormal values at baseline. IgG, IgA, IgG1 and IgG3 serum levels decreased albeit within the normal range. The frequency of CD4+CD45RA+CCR7+ naïve T cells increased. CONCLUSIONS: In vivo blockade of the IL-6 receptor decreases lymphocyte activation and restores B and T cell homoeostasis by either blocking differentiation and/or trafficking in patients with SLE and leads to normalisation of the abnormal B and T cell subsets seen at baseline.

Complexes of Ag and ZnO nanoparticles with BBR for enhancement of gastrointestinal antibacterial activity through the impacts of size and composition.

This study introduces the bioformulations of Ag/BBR and ZnO/BBR complexes against pathogenic bacteria in the gastrointestinal tract. Without the use of toxic reduction agents, Ag and ZnO NPs were prepared using an electrochemical method and then facially mixed with BBR solution to form Ag/BBR and ZnO/BBR complexes. BBR molecules are strongly conjugated with Ag and ZnO NPs through coordinated bonding and electrostatic interaction. As a result, the presence of BBR significantly influenced the nanoparticle growth, resulting in the formation of core/shell structured Ag/BBR and ZnO/BBR NPs with small particle sizes. The antibacterial test showed that BBR, Ag, or ZnO components all contributed to the increase of antibacterial ability of Ag/BBR and ZnO/BBR NPs against both methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella enteritidis (S. enteritidis). The bactericidal ability of Ag/BBR and ZnO/BBR complexes against MRSA was exhibited even at a concentration of four-fold dilution (corresponding to 1.25 g L-1 of BBR and 46.25 mg L-1 of Ag) and two-fold dilution (corresponding to 2.5 g L-1 of BBR and 10 mg L-1 of ZnO), respectively, while that of the Ag/BBR complex against S. enteritidis showed at a concentration of two-fold dilution corresponding to 2.5 g L-1 of BBR and 92.5 mg L-1 of Ag. The results obtained in this study support that Ag/BBR and ZnO/BBR complexes can be potential therapeutic agents against gastrointestinal infections.