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This paper describes a convenient and straightforward method developed to extract keratin particles (KPs) from human hair. It also involves their characterization by several methods and encapsulation of the anticancer drug Paclitaxel (Taxol) within them, aiming for targeted delivery to cancerous sites and slow release at their vicinity. The KPs obtained were in micrometer in size. They are capable of encapsulating Taxol within them with a high encapsulation efficiency of 56% and a drug loading capacity of 2.360 g of Taxol per g keratin. As revealed by the SEM elemental analysis, KPs do not contain any toxic metal ion, and hence, they pose no toxicity to human cells. The pH-dependent release kinetics of the drug from KPs indicates that the drug is released faster when the pH of the solution is increased in the 5.0 to 7.0 pH range. The release kinetics obtained is impressive, and once targeted to the cancerous sites, using cancer directing agents, such as folic acid; a glutamate urea ligand known as DUPA; aminopeptidase N, also known as CD13; and FAP-α-targeting agents, the slow release of the drug is expected to destroy only the cancerous cells. The Noyes-Whitney dissolution model was used to analyze the release behavior of Taxol from KPs, which shows excellent fitting with experimental data. The pH dependence of drug release from keratin is also explained using the 3-D structures and keratin stability at different pH values. [ABSTRACT FROM AUTHOR]

Introduction. Human ABO blood type antigens exhibit alternative phenotypes and genetically derived glycoconjugate structures that are located on the red cell surface which play an active role in the cells' physiology and pathology. Associations between the blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. However, due to lack of antigens of some blood groups, there have been some contentious issues with the association between the ABO blood group and vulnerability to certain infectious and noninfectious diseases. Objective. To review different literatures that show the association between ABO blood groups and different diseases. Method. Original, adequate, and recent articles on the same field were researched, and the researcher conducted a comprehensive review on this topic. Thus, taking out critical discussions, not only a descriptive summary of the topic but also contradictory ideas were fully retrieved and presented in a clear impression. In addition, some relevant scientific papers published in previous years were included. The article search was performed by matching the terms blood types/groups with a group of terms related to different diseases. The articles were screened and selected based on the title and abstract presented. Results. The susceptibility to various diseases, such as cancer, cardiovascular diseases, infections and hematologic disorders, cognitive disorders, circulatory diseases, metabolic diseases, and malaria, has been linked with ABO blood groups. Moreover, blood group AB individuals were found to be susceptible to an increased risk of cognitive impairment which was independent of geographic region, age, race, and gender. Disorders such as hypertension, obesity, dyslipidemia, cardiovascular disease (CVD), and diabetes were also more prevalent in individuals with cognitive impairment. Early etiological studies indicated that blood type O has a connection with increased incidence of cholera, plague, tuberculosis infections, and mumps, whereas blood type A is linked with increased incidence of smallpox and Pseudomonas aeruginosa infection; blood type B is also associated with increased incidence of gonorrhea, tuberculosis, and Streptococcus pneumoniae, E. coli, and salmonella infections; and blood type AB is associated with increased incidence of smallpox and E. coli and salmonella infections. Diabetes mellitus, hypercholesterolemia, arterial hypertension, and family history for ischemic heart disease are the most common risk factors for cardiovascular diseases and can be genetically transmitted to offspring. Higher incidence of cancers in the stomach, ovaries, salivary glands, cervix, uterus, and colon/rectum was common in blood type A people than in O type people. The link between the ABO blood type and thromboembolic diseases and bleeding risk are intervened by the glycosyltransferase activity and plasma levels and biologic activity of vWF (Von Willebrand factor), a carrier protein for coagulation factor VIII which is low in O type. Conclusion. Several studies related to the ABO phenotype show that genetically determined human ABO blood groups were correspondingly linked with an increased risk of various infectious and noninfectious diseases. However, further investigations are needed particularly on the molecular level of ABO blood groups and their association with various diseases. [ABSTRACT FROM AUTHOR]

The body's autoimmune process is involved in the development of Graves' disease (GD), which is manifested by an overactive thyroid gland. In some patients, autoreactive inflammatory reactions contribute to the development of symptoms such as thyroid ophthalmopathy, and the subsequent signs and symptoms are derived from the expansion of orbital adipose tissue and edema of extraocular muscles within the orbit. The autoimmune process, production of antibodies against self-antigens such as TSH receptor (TSHR) and IGF-1 receptor (IGF-1R), inflammatory infiltration, and accumulation of glycosaminoglycans (GAG) lead to edematous-infiltrative changes in periocular tissues. As a consequence, edema exophthalmos develops. Orbital fibroblasts seem to play a crucial role in orbital inflammation, tissue expansion, remodeling, and fibrosis because of their proliferative activity as well as their capacity to differentiate into adipocytes and myofibroblasts and production of GAG. In this paper, based on the available medical literature, the immunological mechanism of GO pathogenesis has been summarized. Particular attention was paid to the role of orbital fibroblasts and putative autoantigens. A deeper understanding of the pathomechanism of the disease and the involvement of immunological processes may give rise to the introduction of new, effective, and safe methods of treatment or monitoring of the disease activity. [ABSTRACT FROM AUTHOR]

Sitagliptin is a member of a class of drugs that inhibit dipeptidyl peptidase (DPP-4). It increases the levels of the active form of incretins such as GLP-1 (glucagon-like peptide-1) or GIP (gastric inhibitory polypeptide) and by their means positively affects glucose metabolism. It is successfully applied in the treatment of diabetes mellitus type 2. The most recent scientific reports suggest beneficial effect of sitagliptin on diseases in which neuron damage occurs. Result of experimental studies may indicate a reducing influence of sitagliptin on inflammatory response within encephalon area. Sitagliptin decreased the levels of proinflammatory factors: TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), IL-17 (interleukin-17), and CD-163 (cluster of differentiation 163), and contributed to an increase in levels of anti-inflammatory factors: IL-10 (interleukin-10) and TGF-β (transforming growth factor β). Moreover, sitagliptin demonstrated antioxidative and antiapoptotic properties by modifying glutamate and glutathione levels within the region of hippocampus in mice. It has been observed that sitagliptin decreases accumulation of β-amyloid within encephalon structures in experimental models of Alzheimer’s dementia. This effect may be connected with SDF-1α (stromal cell-derived factor 1α) concentration. Administration of sitagliptin caused a significant improvement in MMSE (Mini–Mental State Examination) tests used for assessment of dementias. The paper presents potential mechanisms of sitagliptin activity in conditions connected with neuroinflammation with special emphasis on Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Tracking cells and proteins’ phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique’s ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes. [ABSTRACT FROM AUTHOR]

Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains. Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope). The phenomenon of cross-reactivity in HLA testing, often explained as cross-reactive groups (CREGs) of antigens with antibody, can be clearly explained now by public epitopes. Since 2006, we defined and reported 194 HLA class I unique epitopes, including 56 cryptic epitopes on dissociated HLA class I heavy chains, 83 HLA class II epitopes, 60 epitopes on HLA-DRB1, 15 epitopes on HLA-DQB1, 3 epitopes on HLA-DQA1, 5 epitopes on HLA-DPB1, and 7 MICA epitopes. In this paper, we provide a summary of our findings. [ABSTRACT FROM AUTHOR]

Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza. [ABSTRACT FROM AUTHOR]

Identification of B-cell epitopes is a fundamental step for development of epitope-based vaccines, therapeutic antibodies, and diagnostic tools. Epitope-based antibodies are currently the most promising class of biopharmaceuticals. In the last decade, in-depth in silico analysis and categorization of the experimentally identified epitopes stimulated development of algorithms for epitope prediction. Recently, various in silico tools are employed in attempts to predict B-cell epitopes based on sequence and/or structural data. The main objective of epitope identification is to replace an antigen in the immunization, antibody production, and serodiagnosis. The accurate identification of B-cell epitopes still presents major challenges for immunologists. Advances in B-cell epitope mapping and computational prediction have yielded molecular insights into the process of biorecognition and formation of antigen-antibody complex, which may help to localize B-cell epitopes more precisely. In this paper, we have comprehensively reviewed state-of-the-art experimental methods for B-cell epitope identification, existing databases for epitopes, and novel in silico resources and prediction tools available online. We have also elaborated new trends in the antibody-based epitope prediction. The aim of this review is to assist researchers in identification of B-cell epitopes. [ABSTRACT FROM AUTHOR]

MHC molecule plays a key role in immunology, and the molecule binding reaction with peptide is an important prerequisite for T cell immunity induced. MHC II molecules do not have conserved residues, so they appear as open grooves. As a consequence, this will increase the difficulty in predicting MHC II molecules binding peptides. In this paper, we aim to propose a novel prediction method for MHC II molecules binding peptides. First, we calculate sequence similarity and structural similarity between different MHC II molecules. Then, we reorder pseudosequences according to descending similarity values and use a weight calculation formula to calculate new pocket profiles. Finally, we use three scoring functions to predict binding cores and evaluate the accuracy of prediction to judge performance of each scoring function. In the experiment, we set a parameter α in the weight formula. By changing α value, we can observe different performances of each scoring function. We compare our method with the best function to some popular prediction methods and ultimately find that our method outperforms them in identifying binding cores of HLA-DR molecules. [ABSTRACT FROM AUTHOR]

The properties of biomaterials, including their surface microstructural topography and their surface chemistry or surface energy/wettability, affect cellular responses such as cell adhesion, proliferation, and migration. The nanotopography of moderately rough implant surfaces enhances the production of biological mediators in the peri-implant microenvironment with consequent recruitment of differentiating osteogenic cells to the implant surface and stimulates osteogenic maturation. Implant surfaces with moderately rough topography and with high surface energy promote osteogenesis, increase the ratio of bone-to-implant contact, and increase the bonding strength of the bone to the implant at the interface. Certain features of implant surface chemistry are also important in enhancing peri-implant bone wound healing. It is the purpose of this paper to review some of the more important features of titanium implant surfaces which have an impact on osseointegration. [ABSTRACT FROM AUTHOR]

Identification of epitopes which invokes strong humoral responses is an essential issue in the field of immunology. Various computational methods that have been developed based on the antigen structures and the mimotopes these years narrow the search for experimental validation. These methods can be divided into two categories: antigen structure-based methods and mimotope-based methods. Though new methods of the two kinds have been proposed in these years, they cannot maintain a high degree of satisfaction in various circumstances. In this paper, we proposed a new conformational B-cell epitope prediction method based on antigen preprocessing and mimotopes analysis. The method classifies the antigen surface residues into “epitopes” and “nonepitopes” by six epitope propensity scales, removing the “nonepitopes” and using the preprocessed antigen for epitope prediction based on mimotope sequences. The proposed method gives out the mean F score of 0.42 on the testing dataset. When compared with other publicly available servers by using the testing dataset, the new method yields better performance. The results demonstrate the proposed method is competent for the conformational B-cell epitope prediction. [ABSTRACT FROM AUTHOR]

High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]

Background. CD8+ T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+ T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Methods. This preliminary investigation comprised 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies, and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+ T cells were divided into naïve, central memory (CM), effector memory CD45RA- (EM), and effector memory CD45RA+ (EMRA) cells. Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls. Conclusions. The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+ T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings. [ABSTRACT FROM AUTHOR]