Human Defense System Research Articles

Tonsillar Microbiota: a Cross-Sectional Study of Patients with Chronic Tonsillitis or Tonsillar Hypertrophy.

ABSTRACTChronic tonsillitis (CT) and tonsillar hypertrophy (TH) are common tonsillar diseases that are related to infection and inflammation. Little is known about tonsillar microbiota and its role in CT and TH. This study aims to identify palatine tonsillar microbiota both on the surface and in the core tissues of CT and TH patients. In total, 22 palatine tonsils were removed and collected from CT and TH patients who underwent surgery. The surface and core microbiota in the tonsils of CT and TH patients were compared using 16S rRNA gene sequencing of V3-V4 regions. Differential tonsillar microbiotas were found in the CT versus TH patients and surface versus core tissues. Further, a higher relative abundance of bacterial genera, including Haemophilus, Streptococcus, Neisseria, Capnocytophaga, Kingella, Moraxella, and Lachnospiraceae [G-2] in patients with TH and Dialister, Parvimonas, Bacteroidales [G-2], Aggregatibacter, and Atopobium in patients with CT, was observed. Of these, the differential genera of Dialister, Parvimonas, and Neisseria served as key factors in the tonsillar microbiota network. Notably, four representable tonsillar microbial types were identified, with one, consisting of a higher abundance of Haemophilus and Neisseria, exclusively detected in the TH patients. This study analyzed the different tonsillar microbiota from the surface and core tissues of CT and TH patients. Several bacteria and various microbial types related to CT and TH were identified, along with potential bacterial networks and related immune pathways.IMPORTANCE The human microbiota has been shown to be functionally connected to infectious and inflammation-related diseases. So far, only limited studies had been performed on tonsillar microbiota, although tonsils play an essential role in the human immune defense system and encountered numerous microorganisms. Our work presented different tonsillar microbiota from surface and core tissues of chronic tonsillitis (CT) and tonsillar hypertrophy (TH) patients. Notably, one tonsillar microbiota type, which contains a higher abundance of Haemophilus and Neisseria, was only detected in the TH patients. Furthermore, certain bacteria, such as Haemophilus, Neisseria, Dialister, and Parvimonas, may serve as microbial biomarkers to discriminate CT patients from TH patients. These data provide important microbiota data in the tonsillar research area and are highly useful for researchers both in the oral microbiome field and clinical field.

Immunological aspects related to diseases incident in dental practice: Literature review

The microbiome of the human body is home to an extensive community of microorganisms that interact with the immunologically competent host, and may even favor its physiological actions. However, these microbial colonies have potential for harmfulness, including that present in the oral cavity, being able to express themselves intensely in cases of momentary or chronic misadjustment of the human defense system. The diseases with the highest incidence in the oral cavity, periodontitis and dental caries, are pathological processes with microbial involvement and have in the patient’s immune system a great combatant to its development, either as a preventive barrier or with direct actions of defensive response. Both pathological conditions were pointed out in this article, extolling the need for the dentist to observe the immunological aspects of impact on oral health. A bibliographic survey was conducted delimited by the theme- the immunological aspects that impact dental practice, through the databases of the digital platforms Google Academic and PubMed; for the realization of this literature review. Based on the scientific notes raised by this work, we suggest the perspective that; the analysis of immunological aspects associated with the proposed dental diagnoses and treatments may offer a complementation of arguments and approaches that could be much more assertive and effective in the clinical routine.

Microbes, helminths, and rheumatic diseases.

There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood.The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.

RNA Interference: Antiviral Defense Mechanism and Immune Memory

A review of the mechanisms of the generation of antiviral immunity in bacteria, plants, invertebrates, and vertebrates directly indicates the leading role of innate immunity. Bornovirus infections in mammals have been proven to be inhibited by the RNA interference mechanism. Authors propose a possible role of innate human immunity in combating viral infections, including SARS-Cov2. This hypothesis is based on the notion that antiviral response involves a molecular mechanism of RNA interference stemming from the specific viral patterns incorporated into host cells’ DNA. Innate immunity plays an important role not only at the first encounter with a viral infection, but also fully participates in the formation of specific immune memory. RNA-interference along with interferon system is integral parts of human anti-viral defense system. The joint work of these systems is considered. Caution is warranted in both PCR testing interpretation and in assessing prospective vaccines. False positive result without any clinical presentation of the disease in some people might mean that PCR test was picking up any specific SARS-Cov2 sequences that already had incorporated into asymptomatic person’s cellular DNA due to the possible RNA-interference based anti-viral immunity. Future vaccines aimed at producing specific antibodies can cause the phenomenon of antibody-dependent enhancement (ADE) of the infection. In ADE virus not only infects susceptible cells through appropriate receptor, but is able to highjack virus-specific antibodies to easily traffic virus bodies inside the monocytes/macrophages, granulocytes, platelets, mast and many more host cells through interaction with Fc and/or complement receptors. It is necessary to draw the attention of medical community, especially practitioners to the role of innate immunity, which is especially important in the current COVID-19 pandemic.

Hijacking of immune defences by biofilms: a multifront strategy

Biofilm formation by pathogens and opportunistic bacteria is the basis of persistent or recurrent infections. Up to 80% of bacterial infections in humans are associated with biofilms. Despite the efficiency of the evolved and complex human defence system against planktonic bacteria, biofilms are capable of subverting host defences. The immune system is not completely effective in opposing bacteria and preventing infection. Increasing attention is being focussed on the mechanisms enabling bacterial biofilms to skew the coordinate action of humoral and cell mediated responses. Knowledge of the interactions between biofilm bacteria and the immune system is critical to effectively address biofilm infections, which have multiplied over the years with the spread of biomaterials in medicine. In this article, the latest information on the interactions between bacterial biofilms and immune cells is examined and the areas where of information is still lacking are explored.

Bacterial resistance to antimicrobial peptides.

Antimicrobial peptides (AMPs) or host defense peptides (HDPs) are vital components of human innate defense system targeting human-related bacteria. Many bacteria have various mechanisms interfering with AMP activity, causing resistance to AMPs. Since AMPs are considered as potential novel antimicrobial drugs, understanding the mechanisms of bacterial resistance to direct killing of AMPs is of great significance. In this review, a comparative overview of bacterial strategies for resistance to direct killing of various AMPs is presented. Such strategies include bacterial cell envelope modification, AMP degradation, sequestration, expelling, and capsule.

Glutathione Induced Immune-Stimulatory Activity by Promoting M1-Like Macrophages Polarization via Potential ROS Scavenging Capacity.

The present study investigated the immunomodulatory activity of reduced glutathione (GSH) by assessment of the macrophage polarization (MP)-mediated immune response in RAW 264.7 cells. Furthermore, we identified the signal pathway associated with immune regulation by GSH. The expressions of MP-associated cytokines and chemokines were assessed using cytokine array, nCounter Sprit platform, ELISA and immunoblotting. Phagocytosis activity and intracellular reactive oxygen species (ROS) generation were measured using fluorescence-activated cell sorter. As results of the cytokine array and nCounter gene array, GSH not only up-regulated pro-inflammatory cytokines, including interleukins and tumor necrosis factor-α, but also overexpressed neutrophil-attracting chemokines. Furthermore, GSH significantly stimulated the production of immune mediators, including nitric oxide and PGE2, as well as phagocytosis activity through nuclear factor kappa B activation. In addition, GSH significantly decreased LPS-induced ROS generation, which was associated with an activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/ heme oxygenease-1 (HO-1) signaling pathway. Our results suggest that GSH has potential ROS scavenging capacity via the induction of Nrf2-mediated HO-1, and immune-enhancing activity by regulation of M1-like macrophage polarization, indicating that GSH may be a useful strategy to increase the human defense system.

The Role of Systems Biologic Approach in Cell Signaling and Drug Development Responses-A Mini Review.

The immune system is an integral aspect of the human defense system and is primarily responsible for and involved in the communication between the immune cells. It also plays an important role in the protection of the organism from foreign invaders. Recent studies in the literature have described its role in the process of hematopoiesis, lymphocyte recruitment, T cell subset differentiation and inflammation. However, the specific molecular mechanisms underlying these observations remain elusive, impeding the elaborate manipulation of cytokine sequential delivery in tissue repair. Previously, the discovery of new drugs and systems biology went hand in hand; although Systems biology as a term has only originated in the last century. Various new chemicals were tested on the human body, and studied through observation. Animal models replaced humans for initial trials, but the interactions, response, dose and effect between animals and humans could not be directly correlated. Therefore, there is a need to form disease models outside of human subjects to check the effectiveness and response of the newer natural or synthetic chemicals. These emulate human disease conditions wherein the behavior of the chemicals would be similar in the disease model and humans.

Glutathione peroxidase level in patients with Helicobacter pylori-associated gastritis

Helicobacter pylori (H. pylori) associated with the generation of reactive oxygen species (ROS), with leads to oxidative stress in the gastric mucosa. GPX is one of human antioxidative defense system allows the elimination of excess ROS. A cross-sectional study was in 80 consecutive gastritis patients who came to the endoscopic unit of Adam Malik General Hospital and PermataBunda Hospital in Medan, Indonesia, from May–September 2017, to determine the difference of GPX serum level between positive and negative infected H. pylori. the diagnosis of gastritis used Histopathology. Rapid urease test for diagnosis of H. pylori infection. Serum samples were obtained to determined circulating GPX. It used Univariate and bivariate analysis (Mann Whitney U test). There were 50 patients (62.5%) infected with H. pylori. GPX levels in patients with positive H. pylori gastritis were lower than those of negative H. pylori but did not differ significantly. In conclusion, there were no significant differences in GPX level between positive and negative infected H. pylori patients.

Biological properties and pathogenicity factors of Helicobacter pylori

The unexpected discovery of Helicobacter pylori (H. pylori) has revolutionised the history of microbiology as well as of gastroenterology in the last 30 years, with an invaluable benefit for millions of persons worldwide. The confirmation that this Gram-negative spiral bacterium could live in the stomach has rendered out-of-date the concept of inhospitality of micro-organisms in the gastric environment, after a long history of unheard reports on the presence of spiral bacteria in the stomach. The pathogenicity of H. pylori depends on its ability to colonize as well as the capability to survive in the harsh gastric environment. This is possible by a coevolution between the pathogen itself and the host. Any perturbation of this equilibrium disrupts the host-pathogen interaction, promoting the pathological effects. H. pylori has a wide range of pathogenicity factors, in particular cytotoxins, enzymes of aggression, and factors providing protection against human defense systems. The most well-characterized cytotoxins contributing to epithelial cell damage are the vacuolating cytotoxin A (VacA) and the cytotoxin-associated gene A (CagA). Only detailed knowledge of the microbiology and genomics of H. pylori infection will allow a vaccine to be produced. Today, we know that H. pylori induces strong humoral and cellular immune responses, but these are incapable of eliminating the bacterium, raising doubts about the possibility of developing an effective vaccine easily. This review highlights microbiological findings concerning H. pylori infection, focusing on colonization, survival and pathogenicity.

Host Antimicrobial Peptides: The Promise of New Treatment Strategies against Tuberculosis.

Tuberculosis (TB) continues to be a devastating infectious disease and remerges as a global health emergency due to an alarming rise of antimicrobial resistance to its treatment. Despite of the serious effort that has been applied to develop effective antitubercular chemotherapies, the potential of antimicrobial peptides (AMPs) remains underexploited. A large amount of literature is now accessible on the AMP mechanisms of action against a diversity of pathogens; nevertheless, research on their activity on mycobacteria is still scarce. In particular, there is an urgent need to integrate all available interdisciplinary strategies to eradicate extensively drug-resistant Mycobacterium tuberculosis strains. In this context, we should not underestimate our endogenous antimicrobial proteins and peptides as ancient players of the human host defense system. We are confident that novel antibiotics based on human AMPs displaying a rapid and multifaceted mechanism, with reduced toxicity, should significantly contribute to reverse the tide of antimycobacterial drug resistance. In this review, we have provided an up to date perspective of the current research on AMPs to be applied in the fight against TB. A better understanding on the mechanisms of action of human endogenous peptides should ensure the basis for the best guided design of novel antitubercular chemotherapeutics.

Molecular Interactions of Carcinogenic Aromatic Amines, 4-Aminobiphenyl and 4,4’-Diaminobiphenyl, with Lactoperoxidase – Insight to Breast Cancer

Lactoperoxidase (LPO) is an antimicrobial protein present in milk, saliva, gastric secretions, tears and upper respiratory tract secretions. LPO constitutes an important enzyme of the human immune defense system. However, LPO has also been suggested to be involved in breast cancer etiology through production of reactive free radicals and activation of carcinogenic aromatic compounds. Aromatic compounds are generally highly lipophilic and thus accumulate in highly fatty breast tissues. The aromatic compounds 4-aminobiphenyl (ABP) and 4,4'-diaminobiphenyl (BZ) are known to have carcinogenic properties. LPO catalyzes their oxidation and converts them into reactive products which bind to DNA and form adducts. These DNA adducts subsequently lead to breast cancer. The crystal structure of LPO was obtained from Protein Data Bank. Structures of ABP and BZ were retrieved from PubChem database. Induced Fit Docking was performed using glide module from Schrodinger. The present study reports the structural binding of ABP and BZ with LPO using in silico approaches. The amino acid residues of LPO involved in the binding with the two aromatic ligands were characterized and binding energy values were calculated. Both ABP and BZ were placed in the substrate binding site present in the distal heme cavity of LPO with good affinity. The binding mode mimicked that of the natural substrate since these compounds did not disturb the water molecule that plays an important role in the oxidation reaction. Thus, the water molecule is potentially available for facilitating the subsequent activation of the aromatic amines to reactive species which may form DNA adducts leading to breast cancer.

Abstract 2995: Development of a novel highly potent TLR8 selective agonist for cancer immunotherapy

Abstract The cancer drug discovery field is experiencing unprecedented revolution accompanied by growing excitement from researchers, drug developers, patients and investors, partly due to recent clinical success of cancer immunotherapy. Human immune defense system comprises both innate and adaptive immune pathways. All the targets drugged by the recently approved cancer immunotherapeutic agents including the immune checkpoint proteins PD-1, PD-L1 and CTLA-4 function in adaptive immune pathways. In contrast, targets involved in the innate immune pathway have not matured to regulatory approval for systemic use though several candidates are now in preclinical and clinical development. Drugs targeting innate immunity represent great opportunity for more rapid and broader spectrum anti-cancer effect than adaptive immunity. Furthermore, combinations of drugs targeting innate and adaptive immunity are expected to produce strong synergistic efficacy owing to their complementary nature as body’s immune defense. Toll-like receptors (TLRs) are a family of proteins that recognize pathogen associated molecular patterns (PAMPs). Their primary function is to activate innate immune responses while also involved in facilitating adaptive immune responses. Different TLRs exert distinct functions by activating varied immune cascades. TLR8 is more broadly expressed in immune cells than other TLRs such as TLR7 and TLR9. One of the major causes of cancer immunotherapy failure is potent suppression of immune response by Treg cells. TLR8 is the only TLR that has been shown to be necessary and sufficient to reverse the suppressive function of Treg cells leading to strong tumor inhibition. Therefore, agonists targeting TLR8 are expected to be effective cancer therapy. However, there is no approved TLR8 selective agonist at present. There is only one TLR8 selective agonist in clinical development. Through structure-based drug design, we discovered a novel, highly potent and selective small molecule TLR8 agonist, DN-A1. DN-A1 exhibited strong in vitro cellular activity with EC50 at 4.23 nM, about 30-fold more potent than the only drug candidate in clinical trials. The activity was highly selective for TLR8 over other TLRs. DN-A1 displayed superior in vitro ADMET and in vivo PK profiles. DN-A1 showed clean CYP profile with IC50 over 10 μM for all major CYP isoenzymes tested including 3A4, 1A2, 2C9, 2C19 and 2D6. DN-A1 had favorable hERG parameter with IC50 over 30 μM whereas the reference compound’s hERG IC50 was 3.84 μM suggesting potential cardiac toxicity. DN-A1 significantly impeded tumor growth as a single agent and was well-tolerated in mouse tumor models. Taken together, DN-A1 warrants further development as a potential best-in-class preclinical drug candidate for TLR8-mediated cancer immunotherapy. Citation Format: Yuxun Wang, Heping Yang, Longsheng Wang, Guangliang Fu, Fang Bao, Fang Liu, Shuwen Ren, Huanping Li, Haixia Ji, Yajun Yu, Zhiheng Wu, Panhu Zhu, Hui Xu, Yaqiao Gao, Pei Wang, Shoujun Chen, Daxin Gao. Development of a novel highly potent TLR8 selective agonist for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2995. doi:10.1158/1538-7445.AM2017-2995

“More Human Than Human”: “Flattening of Affect,” Synthetic Humans, and the Social Construction of Maleness

We're all schizophrenic, with defective emotional lives--flattening of affect, it's called. What I've done ... that's become alien to me. In fact everything about me has become unnatural; I've become an unnatural self. Philip K. Dick Do Androids Dream of Electric Sheep? In Philip k. dick's novel, androids are unable to empathize with or feel for others. Their absence of spontaneous emotional response to hypothetical scenarios is the diagnostic used to distinguish them from humans. Androids' disconnection from others and lack of response constitute the affective to which Pris, an android, refers, understood in Dick's novel as a defect that, when unattributable to mental illness, marks one as other than human. Thus, above, Pris lies to her human interlocutor, misattributing the cause of her flattening in order to provide a human explanation for the feature used to identify androids, who are subject to being retired, a euphemism for their summary execution. In this deficit and its implications for human identity, Pris and her fellow androids (andys) are hardly alone. Dick's novel, Ridley Scott's film adaptation, Blade Runner, and (writer) Ronald Moore and (producer) David Eick's recent Battlestar Galactica television series are a few examples of a trend that proliferates from the 1950s onwards. (1) In such science-fiction texts, humans build and often come into conflict with beings that have been created by humans or have evolved from those created by humans. These beings are almost indistinguishable from humans, except, of course, for that all-important lack of emotional connection: that necessary flattening of affect. While critics generally frame such texts as questioning the nature of the human, (2) they represent specifically gendered anxieties. Synthetic humans are distinguished from humans by a particular form of emotional insufficiency. While they usually do feel, they generally lack abilities to know and understand their feelings, feel in relation to others, and/or empathize with or understand the feelings of others. Commenting on the historical shift in the attributes characterizing synthetic humans, Despina Kakoudaki argues that If for Descartes ... automata differ from people because they have ... no reason, by the early twentieth century artificial people differ from real people because all they have is (181). Andys, replicants, and Galacticas Cylons can all have implanted memories, which means that characters can be synthetic without knowing it. Given that the shift Kakoudaki identifies undermines modernity's ideal of the human-as-rational-subject, it is unsurprising that the Galactica character who most persistently questions whether or not he is a Cylon is Gaius Baltar, whom we initially meet as a scientist with an important role in the human Colonies' defense system and who places great stock in his own rationality. Both Baltar's investment in rationality and his sex are relevant; given white, Western maleness's (and normative masculinity's) association with logic, reason, and denying and flattening affect and femaleness's (and normative femininity's) with emotionality, emotional intelligence, and empathy, any sense that emotionality defines the human has gendered implications. Modernity's rational subject, associated with Enlightenment ideals and the Classical traditions they draw on, is one whose maleness, Westernness, and whiteness has historically been used as the measure against which disenfranchised groups, including women, people of colour, and the colonized, have fallen short, judged insufficiently rational and overly emotional. It is therefore his identity that comes into question when reason is no longer a guarantor of human identity. As Alison Jagger notes, The western tradition has not seen everyone as equally emotional. Instead, reason has been associated with members of dominant political, social, and cultural groups and emotion with members of subordinate groups. …

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+), suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.

The duration of disgusted and fearful faces is judged longer and shorter than that of neutral faces: the attention-related time distortions as revealed by behavioral and electrophysiological measurements.

Time perception has been shown to be altered by emotions. This study employed event-related potentials (ERPs) to examine the effects of two threat-related emotions on the judgment of time intervals in the range of 490–910 ms. We demonstrated that disgust and fear have distinct influences on time perception. At the behavioral level, disgusted faces were estimated longer and fearful faces were estimated shorter (i.e., the generalization gradient for the disgusted faces was shifted left while the generalization gradient for the fearful faces was shifted right) when compared with neutral faces. Accordingly, the contingent negative variation, an online ERP index of timing, displayed larger area in disgust and smaller area in fear conditions when compared with neutral condition (disgust = 1.94 ± 2.35 μV•s, neutral = 1.40 ± 2.5 μV•s, and fear = 1.00 ± 2.26 μV•s). These findings indicated that specific neural mechanisms may underlie the attention effects of different subtypes of threat-related emotions on timing; compared with neutral faces, fearful faces are likely to attract more attentional resources while disgusted faces may attract less attentional resources for emotional processing. The major contribution of the current study is to provide neural correlates of fear vs. disgust divergence in the aspect of time perception and to demonstrate beyond the behavioral level that the categorization of threat-related emotions should be refined so to highlight the adaptability of the human defense system.

Cancer wars: significance of protein unfolding in cancer and its inhibition with natural amphiphilic substances.

OPINION article Front. Oncol., 11 July 2014 | https://doi.org/10.3389/fonc.2014.00183

The role of glycans in immune evasion: the human fetoembryonic defence system hypothesis revisited.

Emerging data suggest that mechanisms to evade the human immune system may be shared by the conceptus, tumour cells, persistent pathogens and viruses. It is therefore timely to revisit the human fetoembryonic defense system (Hu-FEDS) hypothesis that was proposed in two papers in the 1990s. The initial paper suggested that glycoconjugates expressed in the human reproductive system inhibited immune responses directed against gametes and the developing human by employing their carbohydrate sequences as functional groups. These glycoconjugates were proposed to block specific binding interactions and interact with lectins linked to signal transduction pathways that modulated immune cell functions. The second article suggested that aggressive tumour cells and persistent pathogens (HIV, H. pylori, schistosomes) either mimicked or acquired the same carbohydrate functional groups employed in this system to evade immune responses. This subterfuge enabled these pathogens and tumour cells to couple their survival to the human reproductive imperative. The Hu-FEDS model has been repeatedly tested since its inception. Data relevant to this model have also been obtained in other studies. Herein, the Hu-FEDS hypothesis is revisited in the context of these more recent findings. Far more supportive evidence for this model now exists than when it was first proposed, and many of the original predictions have been validated. This type of subterfuge by pathogens and tumour cells likely applies to all sexually reproducing metazoans that must protect their gametes from immune responses. Intervention in these pathological states will likely remain problematic until this system of immune evasion is fully understood and appreciated.

The Immunologic Properties of Undifferentiated Stem Cells from Human Exfoliated Deciduous Teeth (SHED) and Its Potential Application in Bone Regeneration

Introduction: Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic cells capable of differentiating into osteoblasts and inducing bone formation. It is a potential alternative for stem cell bone regeneration therapy. However, stem cell therapy carries the risk of immune rejection mediated by inflammatory cytokines of the human defense system. Objective: This preliminary research studies the interaction between SHED and the immune system by determining the inflammatory cytokines profile and osteogenic potential of SHED. Methods: Human fetal osteoblasts (hFOb) cell line and isolated SHED were cultured and total RNA was extracted, followed by reverse transcription cDNA synthesis. Semi-quantitative reverse transcription PCR and Multiplex PCR were performed to detect the expression levels of OPG/RANKL and TNF-α, IL-1β, IL-6, IL-8 and TGF-β in both cell types. Results: Analysis showed that SHED expressed significantly lower amounts of IL-1β, IL-6, and IL-8 compared to hFOB. IL-1β is a potent bone-resorbing factor, while IL-6 and IL-8 induce osteoclastogenesis and osteolysis respectively. SHED did not express TNF-α which stimulates osteoclastic activity. SHED demonstrated high OPG/RANKL ratio, in contrast with that of marrow stem cells described in previous studies. Our findings suggest that SHED may have improved immunomodulatory profile in terms of promoting relatively lower inflammatory reaction during transplant and enhancing bone regeneration. Conclusion: SHED has a potential to be a good source of osteoblasts for bone regeneration therapy. Further studies on the immunomodulatory properties of SHED-derived osteoblasts are necessary to enable stem cell therapy in immunocompetent hosts

Crystallization and preliminary X-ray diffraction analysis of a DING protein from Pseudomonas aeruginosa PA14.

DING proteins form an emergent family of proteins consisting of an increasing number of homologues that have been identified in all kingdoms of life. They belong to the superfamily of phosphate-binding proteins and exhibit a high affinity for phosphate. In eukaryotes, DING proteins have been isolated by virtue of their implication in several diseases and biological processes. Some of them are potent inhibitors of HIV-1 replication/transcription, raising the question of their potential involvement in the human defence system. Recently, a protein from Pseudomonas aeruginosa strain PA14, named PA14DING or LapC, belonging to the DING family has been identified. The structure of PA14DING, combined with detailed biochemical characterization and comparative analysis with available DING protein structures, will be helpful in understanding the structural determinants implicated in the inhibition of HIV-1 by DING proteins. Here, the expression, purification and crystallization of PA14DING and the collection of X-ray data to 1.9 Å resolution are reported.