Designing an immunoinformatic vaccine for peri-implantitis using a structural biology approach

ObjectivesPeri-implantitis is a destructive inflammatory process that affects the soft and hard tissues around dental implants. porphyromonas gingivalis, an anaerobic gram-negative bacterium, appears to be the main culprit. Since there is no efficient and specific vaccine to treat peri-implantitis, the goal of our research has been to develop a multi-epitope vaccination utilizing an immunoinformatics approach that targeted P. gingivalis type I fim A.Materials and methodsP. gingivalis peptides 6JKZ and 6KMF are suitable for vaccine development. B- and T-cell epitopes from 6KMF and 6JKZ were detected and evaluated based on critical factors to produce a multi-epitope vaccine construct. It was assessed based on allergenicity, antigenicity, stability. The vaccine's dual major histocompatibility complex (MHC-I and MHC-II) binding epitopes allowed it to reach a larger population. P. gingivalis fimbriae induce immune subversion through TLR -CXCR4 receptor complex pathway. The ClusPro 2.0 server was used to do the molecular docking using TLR2 - CXCR4 and vaccine epitopes as receptor and ligand respectively.ResultsThe designed vaccine was non-allergenic and had a high antigenicity, solubility, and stability. The 3D structure of the vaccine revealed strong interaction with CXCR4(TLR2) using molecular docking. The vaccine-CXCR4 interface was more consistent, possibly because the vaccination has a higher affinity for the CXCR4-TLR2 complex.ConclusionThis study details the vaccine's distinct and sustained interaction with the CXCR4(TLR2) immunological receptor and its consistent and effective utterance in the bacterial system. As a result, our vaccine formulation will evoke a significant memory response and induce an adaptive immune response against P. gingivalis.     

Toxocara Awareness Among Medical Practitioners in Saudi Arabia

Human toxocariasis is a zoonotic infection with global and regional impacts. Worldwide it is underestimated and clinically overlooked. Medical practitioners are generally unaware of the extent of the resulting disease spectrum. The objective of the study was to assess knowledge and disease awareness among medical practitioners in Aseer, south-western Saudi Arabia. A questionnaire addressing knowledge about the parasite, its visceral larva migrans and the disease spectrum generated was used to interview participants. The study included 285 participants. In answer to the question what is toxocara, only 27%, answered correctly that it is a nematode, paediatricians being the majority. With regard to years of experience among participants, 56.8% of those who answered correctly had less than 5-year experience, as opposed to 35.4% for those with more than 10-year experience. The cumulative awareness about the disease manifestations and spectrum, i.e. those who knew, was less than 30% across specialties and years of experiences. Lack of awareness regarding Toxocara infection and the disease spectrum it can generate is evident. The consequence for such lack of knowledge within our practising medical community is simply unacceptable as it might translate into misdiagnosis and consequently misguided treatment.

     

TH1/TH2 chemokines/cytokines profile in rats treated with tetanus toxoid and Euphorbia tirucalli

Natural products, including their purified materials, play a remarkable role in drug development. The Euphorbiaceae family, mainly Euphorbia tirucalli, is used in some traditional medicine, and has evidence that its latex comprises immunomodulatory properties and cytokine production. This study aimed to measure the in vivo production of chemokines (IL-1α, IL-1β, IL-12, and RANTES), T_H1 cytokines (IFN-γ, TNF-α, GM-CSF, and IL-2) and T_H2 cytokines (IL-4, IL-6, IL-10, and IL-13) in rats after treatments with ethanol latex extract of E. tirucalli. Vaccine treated and untreated rats were divided into seven groups to assess antimicrobial activities of the extracted components. After completion of the treatment schedule, blood was withdrawn and sera were collected. The results showed that the main component of the extract was a euphol compound. The extract showed antimicrobial activity and had the ability to modulate innate and adaptive immunity. Animals treated with extract for only 7 days before vaccination showed higher levels of antibody production. The extract showed antibacterial and antifungal activities. The extract could stimulate both adaptive and innate immunity. Pre-treatment with the extract increased immune responses in vaccinated animals, indicating the usefulness of the extract before immunization.     

Pharmacologic Blockade of JAK1/JAK2 Reduces GvHD and Preserves the Graft-Versus-Leukemia Effect

We have recently reported that interferon gamma receptor deficient (IFNγR−/−) allogeneic donor T cells result in significantly less graft-versus-host disease (GvHD) than wild-type (WT) T cells, while maintaining an anti-leukemia or graft-versus-leukemia (GvL) effect after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We demonstrated that IFNγR signaling regulates alloreactive T cell trafficking to GvHD target organs through expression of the chemokine receptor CXCR3 in alloreactive T cells. Since IFNγR signaling is mediated via JAK1/JAK2, we tested the effect of JAK1/JAK2 inhibition on GvHD. While we demonstrated that pharmacologic blockade of JAK1/JAK2 in WT T cells using the JAK1/JAK2 inhibitor, INCB018424 (Ruxolitinib), resulted in a similar effect to IFNγR−/− T cells both in vitro (reduction of CXCR3 expression in T cells) and in vivo (mitigation of GvHD after allo-HSCT), it remains to be determined if in vivo administration of INCB018424 will result in preservation of GvL while reducing GvHD. Here, we report that INCB018424 reduces GvHD and preserves the beneficial GvL effect in two different murine MHC-mismatched allo-HSCT models and using two different murine leukemia models (lymphoid leukemia and myeloid leukemia). In addition, prolonged administration of INCB018424 further improves survival after allo-HSCT and is superior to other JAK1/JAK2 inhibitors, such as TG101348 or AZD1480. These data suggest that pharmacologic inhibition of JAK1/JAK2 might be a promising therapeutic approach to achieve the beneficial anti-leukemia effect and overcome HLA-barriers in allo-HSCT. It might also be exploited in other diseases besides GvHD, such as organ transplant rejection, chronic inflammatory diseases and autoimmune diseases.     

Influence of weather and atmospheric pollution on physical activity in patients with COPD

Rationale

Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.

Methods

Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM₁₀ and ozone (O₃) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.

Results

Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O₃ levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM₁₀ reduced activity (p = 0.018) but not during the weekend.

Conclusions

Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users.     

Effect of melittin on mice stomach

Melittin, the main bee venom component, has many positive biological effects and a relatively low toxicity in various cell types. However, there is no evidence of the effect of melittin on gastrointestinal cells. In the present study, we investigated the histological and immuonohistochemical effects of melittin on mice stomach. Adult male mice (Albino Swiss) were randomly divided into two groups (7 mice for each group): control group and melittin only treated group (10 and 40 μg/kg). These mice were sacrificed, then samples from the stomach were collected and prepared for histopathological studies by using alcian blue stain and immuonohistochemical studies by using smooth muscle actin (SMA) antibody. Treatment with melittin alone do not cause any harmful effect on the stomach tissue where the microscopic examination of Alcian blue stained section showed the normal distribution of the mucous secreting cells of the stomach tissues. On other hand, no changes were observed on smooth muscle cells. This study demonstrated the safety of using melittin on gastrointestinal tissues if used in definite dose and for suitable duration, which offers an opportunity for its use as a treatment for many diseases of the gastrointestinal tract.