Perturbation of cellular immune functions in cigarette smokers and protection by palm oil vitamin E supplementation

Background

Cigarette smoke contains free radicals and an have adverse effect to the immune system. Supplementation of palm oil vitamin E (palmvitee), is known has antioxidant properties is thought to be beneficial for system immune protection against free radicals activity. The objective of the study was to determine the effect of palmvitee supplementation on immune response in smokers.

Methods

This study involved a group of smokers and nonsmokers who received 200?mg/day palmvitee and placebo for the control group. Blood samples were taken at 0, 12 and 24?weeks of supplementation. Plasma tocopherol and tocotrienol were determined by HPLC, lymphocyte proliferation by lymphocyte transformation test (LTT) and enumeration of lymphocytes T and B cells by flow cytometry. Statistical analysis was performed by Mann–Whitney U-test for non-parametric data distribution and correlation among the variables was examined by Spearman.

Results

Plasma tocopherol and tocotrienol were increased in vitamin E supplemented group as compared to placebo group. Urine cotinine levels and serum α₁-antitrypsin were significantly higher in smokers compared to nonsmokers. Lymphocyte proliferation induced by PHA showed an increasing trend with palmvitee supplementation in both smokers and nonsmokers. Natural killer cells were decreased; CD4⁺ cells and B cells were increased in smokers compared to nonsmokers but were unaffected with vitamin E supplementation except in the percentage of B cells which were increased in nonsmokers supplemented palmvitee compared to placebo. CD4⁺/CD8⁺ ratio was increased in smokers compared to nonsmokers. The high TWBC count observed in smokers correlated with the increased CD4⁺ and B cells.

Conclusions

Smoking caused alterations in certain immune parameters and palmvitee supplementation tended to cause an increase in lymphocytes transformation test but had no effect on CD3⁺, CD4⁺, CD8⁺, NK cells and B cells except B cells percentage in nonsmokers.

     

Interleukin-12 is not essential for silicosis in mice

Background  

Silicosis features foci of inflammation where macrophages and lymphocytes precede and accompany fibroblast proliferation, alveolar epithelial hyperplasia, and increased deposition of connective tissue matrix material. In the mouse following silica inhalation there is recruitment of natural killer-, B-, and CD4⁺ and CD8⁺ lymphocytes to the alveolar spaces, enlargement of bronchial-associated lymphoid tissues (BALT), and aggregation of lymphocytes surrounding small airways and blood vessels. A substantial fraction of the recruited lung lymphocytes produce interferon-γ (IFN-γ), and IFN-γ gene-deleted mice develop less silicosis than wild-type mice. Interleukin-12 (IL-12) is an important pathway for driving the adaptive immune response towards a TH1-like phenotype. We hypothesized that IL-12 might stimulate lymphocyte activation and the up-regulation of IFN-γ, and consequently be an essential mediator for silicosis.     

Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype,but Not Their Migration Ability

In mycobacterial infections, the number of cells from two newly discovered subpopulations of CD3⁺ myeloid cells are increased at the infection site; one type expresses the T cell receptor (CD3⁺TCRαβ⁺) and the other does not (CD3⁺TCRαβ⁻). The role of Mycobacterium tuberculosis (Mtb) virulence in generating these subpopulations and the ability of these cells to migrate remains unclear. In this study, monocyte-derived macrophages (MDMs) infected in vitro with either a virulent (H37Rv) or an avirulent (H37Ra) Mtb strain were phenotypically characterized based on three MDM phenotypes (CD3⁻, CD3⁺TCRαβ⁺, and CD3⁺TCRαβ⁻); then, their migration ability upon Mtb infection was evaluated. We found no differences in the frequency of CD3⁺ MDMs at 24 h of infection with either Mtb strain. However, H37Rv infection increased the frequency of CD3⁺TCRαβ⁺ MDMs at a multiplicity of infection of 1 and altered the expression of CD1b, CD1c, and TNF on the surface of cells from both the CD3⁺ MDM subpopulations; it also modified the expression of CCR2, CXCR1, and CCR7, thus affecting CCL2 and IL-8 levels. Moreover, H37Rv infection decreased the migration ability of the CD3⁻ MDMs, but not CD3⁺ MDMs. These results confirm that the CD3⁺ macrophage subpopulations express chemokine receptors that respond to chemoattractants, facilitating cell migration. Together, these data suggest that CD3⁺ MDMs are a functional subpopulation involved in the immune response against Mtb.     

The prevalence of exercise-associated hyponatremia in 24-hour ultra-mountain bikers, 24-hour ultra-runners and multi-stage ultra-mountain bikers in the Czech Republic

Background

To assess the prevalence of exercise-associated hyponatremia (EAH) in two 24-hour mountain bike (MTB) (R1,R2), one 24-hour running (R3) and one multi-stage MTB (R4) races held in the Czech Republic in a cluster of four cross-sectional studies.

Methods

In 27 ultra-mountain bikers (ultra-MTBers), 12 ultra-runners, and 14 multi-stage MTBers, fluid intake, changes (Δ) in body mass, hematocrit, plasma volume, plasma [Na⁺], plasma [K⁺], plasma osmolality, urine [Na⁺], urine [K⁺], urine specific gravity, urine osmolality, K⁺/Na⁺ ratio in urine, transtubular potassium gradient and glomerular filtration rate were measured and calculated. The use of non-steroidal anti-inflammatory drugs and symptoms of EAH were recorded using post-race questionnaires.

Results

Of the 53 finishers, three (5.7%) developed post-race EAH, thereof one (3.7%) ultra-MTBer, one (8.3%) ultra-runner and one (7.1%) multi-stage MTBer. Plasma [Na⁺] decreased significantly (p < 0.001) only in R4. Urine osmolality (R1, R3, R4 p < 0.001; R2 p < 0.05) and glomerular filtration rate (p < 0.001) increased, and body mass decreased in all races (p < 0.05). Δ body mass was inversely related to the number of kilometers achieved (p < 0.001) in R2 where better ultra-MTBers tended to lose more weight. Δ body mass (p < 0.001) and %Δ body mass (p = 0.05) were positively related to lower post-race plasma [Na⁺] in R3 that was associated with increased loss in body mass. Fluid intake was positively related to race performance in R1 and R2 (R1: p = 0.04; R2: p = 0.01) where ultra-MTBers in R1 and R2 who drank more finished ahead of those who drank less. Post-race plasma [Na⁺] was negatively associated with race performance in ultra-MTBers in R2 (p < 0.05), similarly ultra-runners in R3 (p < 0.05) where finishers with more kilometres had lower post-race plasma [Na⁺].

Conclusions

The prevalence of EAH in the Czech Republic was no higher compared to existing reports on ultra-endurance athletes in other countries. Lower plasma [Na⁺] and development of EAH may be attributed to overdrinking, a pituitary secretion of vasopressin, an impaired mobilization of osmotically inactive sodium stores, and/or an inappropriate inactivation of osmotically active sodium.     

Study of the Alkylation of Phenol with Methanol on Zn(H)-Exchanged NaY Zeolites

Abstract  

The gas-phase alkylation of phenol with methanol was studied at 473 K on zeolite NaY exchanged with Zn⁺² (samples Zn(x)NaY) or H⁺ (samples Na(x)HY) cations. Zeolite NaY contained only weak and medium Lewis acid sites. The addition of Zn⁺² formed essentially strong Lewis acid sites. In contrast, the exchange of NaY with H⁺ generated Br?nsted acid sites and decreased the density of Lewis acid sites. Zeolite NaY was inactive at 473 K, but after its exchange with Zn²⁺ efficiently promoted the phenol methylation reaction. Phenol conversion and the selectivities to o- and p-cresols increased with the Zn content in the sample. The exchange of Na⁺ with H⁺ also activated the parent NaY zeolite. At similar phenol conversion levels, Na(x)HY samples formed more anisole and less cresols than Zn(x)NaY. All the Zn(x)NaY and Na(x)HY samples deactivated on stream, but the catalyst activity decay increased with the exchange degree.     

Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4⁺CD25^highFoxp3⁺ (nTregs), CD3⁺CD4⁺HLA⁻G⁺, CD3⁺CD8⁺CD28⁻, CD3⁺CD56⁺, and CD56^bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3⁺CD4⁺HLA⁻G⁺ and CD3⁺CD8⁺CD28⁻ RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3⁺CD56⁺, and patients in remission + natalizumab the highest levels of CD56^bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction.     

Opposing Roles of DCs and iNKT Cells in the Induction of Foxp3 Expression by MLN CD25+CD4+ T Cells during IFNγ-Driven Colitis

We have previously shown that a deficiency of CD1d-restricted invariant natural killer T (iNKT) cells exacerbates dextran sulfate sodium (DSS)-induced colitis in Yeti mice that exhibit IFNγ-mediated hyper-inflammation. Although iNKT cell-deficiency resulted in reduced Foxp3 expression by mesenteric lymph node (MLN) CD4⁺ T cells in DSS-treated Yeti mice, the cellular mechanisms that regulate Foxp3 expression by CD25⁺CD4⁺ T cells during intestinal inflammation remain unclear. We found that Foxp3⁻CD25⁺CD4⁺ T cells expressing Th1 and Th17 phenotypic hallmarks preferentially expanded in the MLNs of DSS-treated Yeti/CD1d knockout (KO) mice. Moreover, adoptive transfer of Yeti iNKT cells into iNKT cell-deficient Jα18 KO mice effectively suppressed the expansion of MLN Foxp3⁻CD25⁺CD4⁺ T cells during DSS-induced colitis. Interestingly, MLN dendritic cells (DCs) purified from DSS-treated Yeti/CD1d KO mice promoted the differentiation of naive CD4⁺ T cells into Foxp3⁻CD25⁺CD4⁺ T cells rather than regulatory T (Treg) cells, indicating that MLN DCs might mediate Foxp3⁺CD25⁺CD4⁺ T cell expansion in iNKT cell-sufficient Yeti mice. Furthermore, we showed that Foxp3⁻CD25⁺CD4⁺ T cells were pathogenic in DSS-treated Yeti/CD1d KO mice. Our result suggests that pro-inflammatory DCs and CD1d-restricted iNKT cells play opposing roles in Foxp3 expression by MLN CD25⁺CD4⁺ T cells during IFNγ-mediated intestinal inflammation, with potential therapeutic implications.     

C3 Deficiency Leads to Increased Angiogenesis and Elevated Pro-Angiogenic Leukocyte Recruitment in Ischemic Muscle Tissue

The complement system is a potent inflammatory trigger, activator, and chemoattractant for leukocytes, which play a crucial role in promoting angiogenesis. However, little information is available about the influence of the complement system on angiogenesis in ischemic muscle tissue. To address this topic and analyze the impact of the complement system on angiogenesis, we induced muscle ischemia in complement factor C3 deficient (C3−/−) and wildtype control mice by femoral artery ligation (FAL). At 24 h and 7 days after FAL, we isolated the ischemic gastrocnemius muscles and investigated them by means of (immuno-)histological analyses. C3−/− mice showed elevated ischemic damage 7 days after FAL, as evidenced by H&E staining. In addition, angiogenesis was increased in C3−/− mice, as demonstrated by increased capillary/muscle fiber ratio and increased proliferating endothelial cells (CD31⁺/BrdU⁺). Moreover, our results showed that the total number of leukocytes (CD45⁺) was increased in C3−/− mice, which was based on an increased number of neutrophils (MPO⁺), neutrophil extracellular trap formation (MPO⁺/CitH3⁺), and macrophages (CD68⁺) displaying a shift toward an anti-inflammatory and pro-angiogenic M2-like polarized phenotype (CD68⁺/MRC1⁺). In summary, we show that the deficiency of complement factor C3 increased neutrophil and M2-like polarized macrophage accumulation in ischemic muscle tissue, contributing to angiogenesis.     

Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-Shotgun?, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males

Purpose  

This study determined the effects of 28 days of heavy resistance exercise combined with the nutritional supplement, NO-Shotgun^?, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers.     

Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH⁺, CD87⁺CD276⁺, and EGF⁺Axl⁺) in smokers. A number of CTCs and CSCs in patients with SCLC have been shown to be resistant to chemotherapy (CT). High cytotoxic activity and resistance to apoptosis of reprogrammed CD3⁺CD8⁺ T-lymphocytes (rTcells) in relation to naive CD3⁺CD8⁺ T-lymphocytes was demonstrated in a smoking patient with SCLC (Patient G) in vitro. The target for rTcells was patient G’s blood CSCs. Reprogramming of CD3⁺CD8⁺ T-lymphocytes was carried out with the MEK1/2 inhibitor and PD-1/PD-L1 pathway blocker nivolumab. The training procedure was performed with a suspension of dead CTCs and CSCs obtained from patient’s G blood. The presented data show a new avenue for personalized SCLC diagnosis and targeted improvement of chemotherapy based on the use of both CTCs and CSCs.     

Efficient Oxidation of 2,3,6-Trimethyl Phenol using Non-Exchanged and H<Superscript>+</Superscript> Exchanged Manganese Oxide Octahedral Molecular Sieves (K-OMS-2 and H–K-OMS-2) as Catalysts

Abstract  

A new and efficient oxidation process of 2,3,6-trimethyl phenol to 2,3,6-trimethyl benzoquinone (TMQ) is reported forthwith using non-exchanged and H⁺-exchanged manganese oxide octahedral molecular sieves (K-OMS-2 and H–K-OMS-2) as benign catalysts. The oxidation reaction is efficiently carried out using TBHP as oxidant and with catalytic amounts of OMS-2 achieving >95% conversion with excellent selectivity (~99%) to TMQ in 30 min.     

Effects of β-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial

Background  

Intermittent bouts of high-intensity exercise result in diminished stores of energy substrates, followed by an accumulation of metabolites, promoting chronic physiological adaptations. In addition, β-alanine has been accepted has an effective physiological hydrogen ion (H⁺) buffer. Concurrent high-intensity interval training (HIIT) and β-alanine supplementation may result in greater adaptations than HIIT alone. The purpose of the current study was to evaluate the effects of combining β-alanine supplementation with high-intensity interval training (HIIT) on endurance performance and aerobic metabolism in recreationally active college-aged men.     

Reciprocal Alterations in Osteoprogenitor and Immune Cell Populations in Rheumatoid Synovia

Rheumatoid arthritis (RA) is chronic, autoimmune joint inflammation characterized by irreversible joint destruction. Besides increased resorption, destruction is a result of decreased bone formation, due to suppressed differentiation and function of the mesenchymal lineage-derived osteoblasts in inflammatory milieu. In this study, we analyzed the cellular composition of synovial tissue from 11 RA and 10 control patients harvested during planned surgeries in order to characterize resident synovial progenitor populations. Synovial cells were released by collagenase, and labeled for flow cytometry by two antibody panels: 1. CD3-FITC, CD14-PE, 7-AAD, CD11b-PECy7, CD235a-APC, CD19-APCeF780; and 2. 7-AAD, CD105-PECy7, CD45/CD31/CD235a-APC, and CD200-APCeF780. The proportions of lymphocytes (CD3⁺, CD19⁺) and myeloid (CD11b⁺, CD14⁺) cells were higher in synovial tissue from the patients with RA than in the controls. Among non-hematopoietic (CD45⁻CD31⁻CD235a⁻) cells, there was a decrease in the proportion of CD200⁺CD105⁻ and increase in the proportion of CD200⁻CD105⁺ cells in synovial tissue from the patients with RA in comparison to the control patients. The proportions of both populations were associated with inflammatory activity and could discriminate between the RA and the controls.     

The effects of EPA and DHA enriched fish oil on nutritional and immunological markers of treatment naïve breast cancer patients: a randomized double-blind controlled trial

Background

We evaluated the effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids enriched fish oil (FO) on nutritional and immunological parameters of treatment naïve breast cancer patients.

Methods

In a randomized double blind controlled trial, the FO group (FG) patients were supplemented with 2 g/ day of FO concentrate containing 1.8 g of n-3 fatty acids during 30 days. The placebo group (PG) received 2 g/ day of mineral oil. At baseline and after the intervention, plasma levels of n-3 fatty acids, dietary intake, weight, body composition, biochemical and immunological markers were assessed.

Results

At the end of the intervention period, no between group differences were observed regarding anthropometric parameters. There was a significant increase in the plasma phospholipid EPA (p = 0.004), DHA (p = 0.007) of the FG patients. In FG patients the percentages of peripheral blood CD4⁺ T lymphocytes and serum high sensitivity C-reactive protein (hsCRP) levels were maintained while in PG patients there was a significant increase in hsCRP (p = 0.024). We also observed a significant reduction in the percentage of CD4⁺ T lymphocytes in the peripheral blood (p = 0.042) of PG patients. No changes in serum proinflammatory cytokine and prostaglandin E₂ levels were observed.

Conclusions

Supplementation of newly diagnosed breast cancer patients with EPA and DHA led to a significant change in the composition of plasma fatty acids, maintained the level of CD4⁺ T cells and serum levels of hsCRP, suggestive of a beneficial effect on the immune system and less active inflammatory response.

Trial registration

Brazilian Clinical Trials Registry (REBEC): RBR-2b2hqh. Registered 29 April 2013, retrospectively registered.

     

The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion

Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8⁺ T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms’ Tumor 1 (WT1) antigen over the disease course (two points at MPE^1st and 2^nd, two months after MPE1^st). Epithelial cell adhesion molecule (EpCAM)⁺ cancer cells (PD-L1⁻ or T cell immunoglobulin mucin-3, TIM-3⁻), both PD-1 or TIM-3 positive CD8⁺ T cells, and CD14⁺CD68⁺CD163⁺TIM-3⁺ macrophages increased from the MPE^1st to MPE^2nd. The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8⁺ T cells and IFN-γ secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (T_CM) of WT1-CTLs was decreased. On the other hand, CD8⁺ T cells in response to SMAD4^P130L, which is homogeneously expressed in EpCAM⁺ cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8⁺ T cell response to SMAD4^P130L was diminished following remarkably decreased numbers of CD8⁺ T_CM in MPE samples. In conclusion, CD8⁺ T cells responding to WT1 or SMAD4^P130L neoantigen expressed in EpCAM⁺ pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment.     

Circular dichroism enhancement by the coordination of different metal ions with a pair of chiral tripodal ligands

The coordination of metal ions with a pair of chiral tripodal ligands (R or S)-2-(2-((bis(pyridin-2-ylmethyl)amino)methyl)phenoxy)-N-(1-phenylethyl)acetamide (R- or S-L) results in the circular dichroism (CD) enhancement distinctly, giving fingerprint information among different metals. Specifically, the CD signals show more obvious magnification upon coordination with Ln^3 + compared with Zn^2 + and other metals. Structural analyses show that in Eu-complex (1), the Eu^3 + metal center is surrounded in a 10-coordinating geometry and the ligand takes fan-like configuration, while in Zn-complex (2), Zn^2 + is surrounded in a 7-coordinating geometry and the ligand takes pincer-like configuration. These differences in the coordination structure as well as intramolecular packing effects are responsible for the variation in CD signal responses of different metal-coordinated systems.     

Catalytic Oxidation of Ammonia to NO over Perovskite-type LaMnO3 and LaVO4 Catalysts

Abstract  

Catalytic oxidation of NH₃ to NO + NO₂ (NO_X) over perovskite-type LaMnO₃ and LaVO₄ prepared by sol–gel was studied. X-ray diffractometry and scanning electron microscopy analyses confirmed that the prepared LaMnO₃ and LaVO₄ had perovskite-type porous structure, and a specific surface area of 33.58 m²/g and 1.2 m²/g for LaMnO₃ and LaVO₄ was measured by BET, respectively. The catalytic oxidation of ammonia to NO_X was found to begin at 350 °C, and approximately 88 and 95% of NH₃ was oxidized to NO_X at 600 °C over LaMnO₃ and LaVO₄, respectively.     

ETS-10 Supported Au Nanoparticles for Solvent-Free Oxidation of 1-Phenylethanol with Oxygen

Abstract  

Au nanoparticles (NPs) were uniformly dispersed on ETS-10 titanosilicate using the cation exchange procedure and [Au(NH₃)₄](NO₃)₃ complex as the gold source. [Au(NH₃)₄]³⁺ cations were first introduced inside ETS-10 micropores, ligands were then released, Au³⁺ was reduced to Au⁺ forming electron-deficient Au clusters, and finally aggregation to Au NPs occurred. In comparison to the incipient-wetness and deposition–precipitation methods, the ion-exchange led to greater activity of the Au NPs in the oxidation of 1-phenylethanol by oxygen.     

Oxidation of Carbon Monoxide Over SBA-15-Confined Copper,Palladium and Iridium Nanocatalysts

Abstract  

Copper, palladium and iridium nanoparticles were synthesised within the pore channels of selectively grafted mesoporous silica SBA-15. The support and catalysts were characterised by different techniques. The synthesized catalyst were able to catalyse oxidation of carbon monoxide with activity values as high as 7.0 × 10⁻³ mmol g⁻¹ cat s⁻¹ at 353 K. Carbon monoxide conversion was found to increase with decreasing nano particle size.