Explore the vast range of titles available.

Passive immunization is the transfer of antibodies and occurs naturally during pregnancy. The transplacental transfer of maternal antibodies to the fetus can protect the infant from many infectious diseases for the first vulnerable months of its life. Passive immunization has been used in the global effort to eliminate maternal and neonatal tetanus. Researchers have estimated that vaccinating pregnant women with two or more doses of tetanus-containing vaccine has reduced neonatal mortality from tetanus by 94%.1In addition, clinicians have used passive immunization, to prevent or to treat various infections for over a century for diseases such as rabies, diphtheria, tetanus, hepatitis B, respiratory syncytial virus and botulism. Passive immunization is also used in immunocompromised individuals and to manage complications after vaccination.

Innovation networks refer to a set of firms and other institutions that work together for a common goal, which is to develop innovation. The importance of these networks in technological fields such as biopharmaceuticals is significant. Accordingly, the purpose of this study is to investigate the role of network capabilities of biopharmaceutical firms in their performance in heterogeneous networks in which they operate. For this purpose, while identifying the main dimensions and components, to answer the research questions, two models were developed. To test the research hypotheses, questionnaires from several biopharmaceutical firms in Iran were analyzed by structural equation modeling. Our results show that network heterogeneity relates to the higher performance of firms in the network, and this relationship is affected by the network capabilities of firms. Also, findings show the moderating and mediating role of network capabilities in the relationship between network heterogeneity and firm performance was confirmed. Finally, the role of networking capabilities, which is mostly related to the main firms (hubs) in this regard, is more prominent.

The demand for recombinant proteins is rising dramatically, and effective production systems are currently being developed. The production of recombinant proteins in plants is a promising approach due to its low cost and low risk of contamination of the proteins with endotoxins or infectious agents from the culture serum. Plant seeds primarily accumulate seed storage proteins (SSPs), which are transcribed and translated from a few genes; therefore, the mechanism underlying SSP accumulation has been studied to help devise ways to increase recombinant protein production. We found that the 3’UTR of SSP genes are essential for SSP accumulation and can be used in the production of recombinant proteins in Arabidopsis . Fusion of the 3’UTR of SSP genes to the 3’ ends of DNA sequences encoding recombinant proteins enables massive accumulation of recombinant proteins with enzymatic activity in Arabidopsis seeds. This method is also applicable to the production of human Interferon Lambda-3 (IFN-lambda 3), a candidate biopharmaceutical compound against hepatitis C infection. Considering the low cost and ease of protein production in Arabidopsis , as well as the rapid growth of this plant, our method is useful for large-scale preparation of recombinant proteins for both academic research and biopharmaceutical production.

The usefulness of higher-order structural information provided by hydrogen/deuterium exchange-mass spectrometry (H/DX-MS) for the structural impact analyses of chemical and post-translational antibody modifications has been demonstrated in various studies. However, the structure–function assessment for protein drugs in biopharmaceutical research and development is often impeded by the relatively low-abundance (below 5%) of critical quality attributes or by overlapping effects of modifications, such as glycosylation, with chemical amino acid modifications; e.g., oxidation or deamidation. We present results demonstrating the applicability of the H/DX-MS technique to monitor conformational changes of specific Fc glycosylation variants produced by in vitro glyco-engineering technology. A trend towards less H/DX in Fc Cγ2 domain segments correlating with larger glycan structures could be confirmed. Furthermore, significant deuterium uptake differences and corresponding binding properties to Fc receptors (as monitored by SPR) between α-2,3- and α-2,6-sialylated Fc glycosylation variants were verified at sensitive levels.

Background Many patients with rare diseases are still lacking a timely diagnosis and approved therapies for their condition despite the tremendous efforts of the research community, biopharmaceutical, medical device industries, and patient support groups. The development of clinical research networks for rare diseases offers a tremendous opportunity for patients and multi-disciplinary teams to collaborate, share expertise, gain better understanding on specific rare diseases, and accelerate clinical research and innovation. Clinical Research Networks have been developed at a national or continental level, but global collaborative efforts to connect them are still lacking. The International Rare Diseases Research Consortium set a Task Force on Clinical Research Networks for Rare Diseases with the objective to analyse the structure and attributes of these networks and to identify the barriers and needs preventing their international collaboration. The Task Force created a survey and sent it to pre-identified clinical research networks located worldwide. Results A total of 34 responses were received. The survey analysis demonstrated that clinical research networks are diverse in their membership composition and emphasize community partnerships including patient groups, health care providers and researchers. The sustainability of the networks is mostly supported by public funding. Activities and research carried out at the networks span the research continuum from basic to clinical to translational research studies. Key elements and infrastructures conducive to collaboration are well adopted by the networks, but barriers to international interoperability are clearly identified. These hurdles can be grouped into five categories: funding limitation; lack of harmonization in regulatory and contracting process; need for common tools and data standards; need for a governance framework and coordination structures; and lack of awareness and robust interactions between networks. Conclusions Through this analysis, the Task Force identified key elements that should support both developing and established clinical research networks for rare diseases in implementing the appropriate structures to achieve international interoperability worldwide. A global roadmap of actions and a specific research agenda, as suggested by this group, provides a platform to identify common goals between these networks.

Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.

The bioactive molecules from microalgae have important properties such as antioxidant, anticancer, antiviral, antibacterial, antihypertensive, skin regenerative, neuroprotective, sunscreen, and, immunostimulatory effects. Bioactive molecules derived from microalgae is getting intense attention from pharmaceuticals, cosmetics and nutraceuticals industries because of these properties and numerous researches have been done to investigate the role of these bioactive molecules that can enlighten microalgal biotechnology to result in new nature derived pharmaceutical formulations. In this study we investigate antioxidant activities of crude extracts of G. Galdieria sulphuraria, Ettlia carotinosa, Neochloris texensis, Chlorella minutissima, Stichococcus bacillaris, Schizochytrium limacinum, Crypthecodinium cohnii, and Chlorella vulgaris with determining radical scavenging activity (RSA) by DPPH (2,2-diphenyl-1-picrylhydrazyl hydrate radical) method and total phenolic content by Folin-Ciocalteu method. Selected extracts according to their antioxidant activities cytotoxicity was evaluated after exposure to human hepatocellular liver carcinoma cells (HepG2) for 48 h. Antioxidant activities of these species ranged from 89 to 95% RSA (radical scavenging activity) while their phenolic contents were also very high, varied from 41 to 312 mg GAE (gallic acid equivalents)/mg extract. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay also showed microalgae has a potential to be used as a novel therapeutic compound.

Human immunoglobulin G isotype 4 (IgG4) antibodies are suitable for use in either the antagonist or agonist format because their low effector functions prevent target cytotoxicity or unwanted cytokine secretion. However, while manufacturing therapeutic antibodies, they are exposed to low pH during purification, and IgG4 is more susceptible to low-pH-induced aggregation than IgG1. Therefore, we investigated the underlying mechanisms of IgG4 aggregation at low pH and engineered an IgG4 with enhanced stability. By swapping the constant regions of IgG1 and IgG4, we determined that the constant heavy chain (CH3) domain is critical for aggregate formation, but a core-hinge-stabilizing S228P mutation in IgG4 is insufficient for preventing aggregation. To identify the aggregation-prone amino acid, we substituted the CH3 domain of IgG4 with that of IgG1, changing IgG4 Arg409 to a Lys, thereby preventing the aggregation of the IgG4 variant as effectively as in IgG1. A stabilizing effect was also recorded with other variable-region variants. Analysis of thermal stability using differential scanning calorimetry revealed that the R409K substitution increased the Tm value of CH3, suggesting that the R409K mutation contributed to the structural strengthening of the CH3-CH3 interaction. The R409K mutation did not influence the binding to antigens/human Fcγ receptors; whereas, the concurrent S228P and R409K mutations in IgG4 suppressed Fab-arm exchange drastically and as effectively as in IgG1, in both in vitro and in vivo in mice models. Our findings suggest that the IgG4 R409K variant represents a potential therapeutic IgG for use in low-effector-activity format that exhibits increased stability.

The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM) for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1). We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101) is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody). Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu). The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier) benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

Persistent ventricular remodeling following myocardial ischemia/reperfusion (MI/R) injury results in functional decompensation and eventual progression to heart failure. VCP979, a novel small-molecule compound developed in-house, possesses anti-inflammatory and anti-fibrotic activities. In the present study, no significant pathological effect was observed following the administration of VCP979 on multiple organs in mice and no difference of aspartate transaminase/alanine aminotransferase/lactate dehydrogenase levels was found in murine serum. Treatment with VCP979 ameliorated cardiac dysfunction, pathological myocardial fibrosis and hypertrophy in murine MI/R injury models. The administration of VCP979 also inhibited the infiltration of inflammatory cells and the pro-inflammatory cytokine expression in hearts post MI/R injury. Further results revealed that the addition of VCP979 prevented the primary neonatal cardiac fibroblasts (NCFs) from Angiotensin II (Ang II)-induced collagen synthesis and neonatal cardiac myocytes (NCMs) hypertrophy. In addition, VCP979 attenuated the activation of p38-mitogen-activated protein kinase in both Ang II-induced NCFs and hearts subjected to MI/R injury. These findings indicated that the novel small-molecule compound VCP979 can improve ventricular remodeling in murine hearts against MI/R injury, suggesting its potential therapeutic function in patients subjected to MI/R injury.