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Human immunodeficiency virus (HIV)/AIDS and cancer coexistence both in vivo and in vitro in a cancer‐immune environment leads to specific cytokines being produced by various immune cells and the cancer cells. Most of the studies have suggested that specific cytokines produced by the immune system cells and the tumor play an important role in the dynamics of non‐Hodgkin lymphomas (NHLs). In this paper, a mathematical model describing the NHL‐immune system interaction in the presence of the HIV, HIV treatment, and chemotherapy is developed. The formulated model, described by nonlinear ODEs, shows existence of multiple equilibria whose stability and bifurcation analysis are presented. From the bifurcation analysis, bistability regions are evident. We observe that with and without HIV treatment, the system results in a nonaggressive tumor size or aggressive tumor (full‐blown tumor) depending on the initial conditions. The results further suggest that at a low endemic state, patients can live for longer period with the tumor, which might explain why some patients can live with cancer for many years. However, initiation of HIV treatment in patients with NHL is observed to lower these endemic states of the tumor. Our results explain why late initiation of HIV treatment might not be helpful to NHL patients. We further investigated the effect of chemotherapy on the dynamics of the tumor. Our simulation results might explain why a few of these chemotherapeutic drugs are more effective when given at a slow continuous rate. The model provides a unique opportunity to influence policy on HIV‐related cancer treatment and management. [ABSTRACT FROM AUTHOR]

We study a mathematical model of immune response by T cells where the regulatory T cells (Treg) inhibit interleukin 2 (IL‐2) secretion. We model the suppression of the autoimmune line of T cells after a different line of T cells responded to a pathogen infection. In this paper, we show that if the population of the pathogen responding line of T cells becomes large enough, the competition for IL‐2 and the increase in the death rates may lead to a depletion in the concentration of autoimmune T cells. Provided this lasts for a sufficiently long time, the concentration of autoimmune T cells can be brought down to values inside the basin of attraction of the controlled state, and autoimmunity can be suppressed. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV)/AIDS and cancer coexistence both in vivo and in vitro in a cancer‐immune environment leads to specific cytokines being produced by various immune cells and the cancer cells. Most of the studies have suggested that specific cytokines produced by the immune system cells and the tumor play an important role in the dynamics of non‐Hodgkin lymphomas (NHLs). In this paper, a mathematical model describing the NHL‐immune system interaction in the presence of the HIV, HIV treatment, and chemotherapy is developed. The formulated model, described by nonlinear ODEs, shows existence of multiple equilibria whose stability and bifurcation analysis are presented. From the bifurcation analysis, bistability regions are evident. We observe that with and without HIV treatment, the system results in a nonaggressive tumor size or aggressive tumor (full‐blown tumor) depending on the initial conditions. The results further suggest that at a low endemic state, patients can live for longer period with the tumor, which might explain why some patients can live with cancer for many years. However, initiation of HIV treatment in patients with NHL is observed to lower these endemic states of the tumor. Our results explain why late initiation of HIV treatment might not be helpful to NHL patients. We further investigated the effect of chemotherapy on the dynamics of the tumor. Our simulation results might explain why a few of these chemotherapeutic drugs are more effective when given at a slow continuous rate. The model provides a unique opportunity to influence policy on HIV‐related cancer treatment and management. [ABSTRACT FROM AUTHOR]

Abstract To date, numerable reviews are found in the literature prominent to the effect of caffeine on the immune system, with the latest review published in 2006. Database screening reveals around three thousand articles that have been published during the last decade. Interestingly, less than hundred articles involved humans and rodents as tested models, out of which 20% is of interest to this paper excluding studies done on the nervous and cardiac systems, and in pregnant and cancer cases. In this review, information pertaining to the experimental setup of various studies, namely, the tested model, the study type (in vivo or in vitro), and caffeine dose is covered to discern the behaviour of major cellular and molecular immune components in light of caffeine exposure. Although it is hard to extrapolate results done in rodents to humans and to relay conclusions from in vitro to in vivo studies, most of the collected data favor the suppressive effects of caffeine on the proliferation of stimulated lymphocytes. Macrophages and natural killer cells also exhibited a reduced activity in the presence of high caffeine doses compared to increased activity at low doses. Immunosuppression is also supported by reduced levels of major anti-inflammatory cytokines, IL-2, IL-6, TNF-α. Moreover, certain innate and adaptive immune receptors, such as TLR1, TLR2, TLR4, and MHC class I-related chain B (MICB) molecules, exhibited decreased expression levels. Thus, we support the use of caffeine to alleviate various inflammatory conditions and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Abstract Mesenchymal stem cells (MSCs) are a population of multipotent cells with the ability of expansion and plastic-adherence in vitro. MSCs can differentiate into chondrocytes, osteocytes and adipocytes; they lack co-stimulatory molecules and have small amount of MHC-I that makes no immunogenicity. These characteristics are empowering MSCs' huge in vivo applications. In addition, MSCs possess the ability of regulating the immune responses in many diseases. Many studies have shown that MSCs have immunosuppressive as well as immunoenhancing properties such as inhibition of T-lymphocytes proliferation and cytokines production which lead to the balance of Th1 and Th2. Some other immunomodulatory features of MSCs are increasing suppressive capacity of T reg , reducing activity of B-lymphocytes and immunoglobulins secretion, inhibition of dendritic cells maturation and antigen presenting capacity, and inhibition of NK-cells activity. MSCs also exert inhibitory effects on neutrophil apoptosis and reduce reactive oxygen species production. The purpose of this paper is to focus on the MSCsʹ effects on immune cells, especially neutrophils. [ABSTRACT FROM AUTHOR]

Irregular and long time work schedules not only makes people feel fatigue, but also brings great risks of diseases, due to gastrointestinal disorder and immune dysfunction. Therefore, it has positive significance to help challenged people stay energetic and healthy with food supplement. Konjac oligosaccharide has shown various physiological benefits and been recommended in the fortification of functional foods. However, there have been few reports on its application aimed to simultaneously relieve physical fatigue and keep body healthy. In this paper, the potential prebiotic, immunoregulatory, and antifatigue activities of konjac oligosaccharide were evaluated in vitro and in vivo. The results showed that konjac oligosaccharide could promote probiotics growth and short chain fatty acids production in mice cecum. At the concentration of 50 to 200 μg/mL, konjac oligosaccharide could activate murine macrophage RAW 264.7 to secret NO and cytokines of IL‐10 and IL‐6. Moreover, this oligosaccharide could alleviate physical fatigue by prolonging exhaustive time, improving the level of superoxide dismutases and glutathione peroxidase, increasing the content of blood glucose, and decreasing the content of blood urea nitrogen. The results suggested that konjac oligosaccharide had prebiotic, immunoregulatory, and antifatigue effects, providing its application potential in functional food aimed at people with irregular and long time work. [ABSTRACT FROM AUTHOR]

Cystectomy is the removal of all or part of the urinary bladder. It has been observed that there is significant regrowth of the bladder after partial cystectomy and this has been proposed to be through regeneration of the organ. Regrowth of tissue in mammals has been proposed to involve compensatory mechanisms that share many characteristics of true regeneration, like the growth of specialized structures such as blood vessels or nerves. However, the overall structure of the normal organ is not achieved. Here we tested if bladder growth after subtotal cystectomy (STC, removal of 50% of the bladder) was compensatory or regenerative. To do this we subjected adult female mouse bladders to STC and assessed regrowth using several established cellular parameters including histological, gene expression, cytokine accumulation and cell proliferation studies. Bladder function was analyzed using cystometry and the voiding stain on paper (VSOP) technique. We found that STC bladders were able to increase their ability to hold urine with the majority of volume restoration occurring within the first two weeks. Regenerating bladders had thinner walls with less mean muscle thickness, and they showed increased collagen deposition at the incision as well as throughout the bladder wall suggesting that fibrosis was occurring. Cell populations differed in their response to injury with urothelial regeneration complete by day 7, but stromal and detrusor muscle still incomplete after 8wks. Cells incorporated EdU when administered at the time of surgery and tracing of EdU positive cells over time indicated that many newborn cells originate at the incision and move mediolaterally. Basal urothelial cells and bladder mesenchymal stem cells but not smooth muscle cells significantly incorporated EdU after STC. Since anti-inflammatory cytokines play a role in regeneration, we analyzed expressed cytokines and found that no anti-inflammatory cytokines were present in the bladder 1wk after STC. Our findings suggest that bladder regrowth after cystectomy is compensatory and functions to increase the volume that the bladder can hold. This finding sets the stage for understanding how the bladder responds to cystectomy and how this can be improved in patients after suffering bladder injury. [ABSTRACT FROM AUTHOR]

Complex Regional Pain Syndrome type 1 (CRPS-1) is a disabling painful disease whose hallmark is pain disproportionate to inciting event. CRPS is also characterized by symptoms and signs, such as vasomotor, sudomotor, trophic and motor changes. Therapeutic approach of CRPS-1 still remains a challenge for clinicians treating a disease with potential heavy consequences on patient prognosis. In the past years, the treatment with bisphosphonates (BPs) has gained some success as confirmed by the results of a number of meta-analyses. The aim of this paper is to point out the pivotal role of bone in CRPS pathogenesis. The efficacy of BPs is likely to be related to bone tissue involvement in the early pathophysiological steps of the disease, as demonstrated by evidences highlighting the central role of bone in the initial phases. Bone can become a source of inflammatory cytokines when triggered by a direct injury. Moreover, peptidergic fibers that innervate both mineralized bone and bone marrow can play a role in triggering or maintaining the microvascular disturbance at bone level. Indeed, bone involvement is consistent with the mineralization disturbance as well as the results of instrumental investigations (e.g., MRI, bone scan). In this regard, an intriguing issue relies on the excellent therapeutic response to BPs treatment of other diseases (e.g., Transient Osteoporosis of the Hip and Regional Migratory Osteoporosis) that share with CRPS-1 some clinical and instrumental features. [ABSTRACT FROM AUTHOR]

Probiotics confer immunological protection to the host through the regulation, stimulation, and modulation of immune responses. Researchers have shifted their attention to better understand the immunomodulatory effects of probiotics, which have the potential to prevent or alleviate certain pathologies for which proper medical treatment is as yet unavailable. It has been scientifically established that immune cells (T- and B-cells) mediate adaptive immunity and confer immunological protection by developing pathogen-specific memory. However, this review is intended to present the recent studies on immunomodulatory effects of probiotics. In the early section of this review, concepts of probiotics and common probiotic strains are focused on. On a priority basis, the immune system, along with mucosal immunity in the human body, is discussed in this study. It has been summarized that a number of species of Lactobacillus and Bifidobacterium exert vital roles in innate immunity by increasing the cytotoxicity of natural killer cells and phagocytosis of macrophages and mediate adaptive immunity by interacting with enterocytes and dendritic, Th1, Th2, and Treg cells. Finally, immunomodulatory effects of probiotics on proinflammatory and anti-inflammatory cytokine production in different animal models have been extensively reviewed in this paper. Therefore, isolating new probiotic strains and investigating their immunomodulatory effects on cytokine profiles in humans remain a topical issue. [ABSTRACT FROM AUTHOR]

Objective: The primary aim of this study was to identify the association between the local inflammatory response in gingival crevicular fluid measured by the levels of multiple proteins and maternal and intra-amniotic inflammatory responses measured by maternal serum C-reactive protein (CRP) and amniotic fluid interleukin (IL)-6 concentrations, respectively, in women with preterm prelabor rupture of membranes (PPROM).Methods: A prospective study was performed in which 78 women with singleton pregnancies complicated by PPROM between 24 + 0 and 36 + 6 weeks of gestation were included. Transabdominal amniocenteses were performed at the time of admission. A bedside assessment of amniotic fluid IL-6 was performed. Maternal serum CRP concentration was also measured at the time of admission. Gingival crevicular fluid was collected from the pocket of the selected tooth (the tooth with the deepest pocket) using standard sterile paper strips within 72 h after admission. Twenty-six proteins in the gingival crevicular fluid were assessed by multiplex the Meso-Scale technology.Results: No correlations between the levels of proteins in the gingival crevicular fluid and maternal serum CRP and amniotic fluid IL-6 concentrations were found, except for a weak positive correlation between granulocyte macrophage colony-stimulating factor and CRP.Conclusions: The local inflammatory response in the gingival crevicular fluid is not related to the maternal and intra-amniotic inflammatory responses in women with PPROM. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem Cells (MSCs) are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency to differentiate into mesodermal cell lineages. The use of MSCs in clinical settings began with high enthusiasm and the number of MSC-based clinical trials has been rising ever since. However; the very unique characteristics of MSCs that made them suitable to for therapeutic use, might give rise to unwanted outcomes, including tumor formation and progression. In this paper, we present a model of carcinogenesis initiated by MSCs, which chains together the tissue organization field theory, the stem cell theory, and the inflammation-cancer chain. We believe that some tissue resident stem cells could be leaked cells from bone marrow MSC pool to various injured tissue, which consequently transform and integrate in the host tissue. If the injury persists or chronic inflammation develops, as a consequence of recurring exposure to growth factors, cytokines, etc. the newly formed tissue from MSCs, which still has conserved their mesenchymal and stemness features, go through rapid population expansion, and nullify their tumor suppressor genes, and hence give rise to neoplastic cell (carcinomas, sarcomas, and carcino-sarcomas). Considering the probability of this hypothesis being true, the clinical and therapeutic use of MSCs should be with caution, and the recipients’ long term follow-up seems to be insightful. [ABSTRACT FROM AUTHOR]

Endometriosis refers to the growth of ectopic endometrial tissue outside the uterine cavity. About 10–15% of female in reproductive age suffer from endometriosis. Several etiologies – such as oxidative stress, inflammatory factors and cytokines, genetic etiology, and hormone role – have been reported for endometriosis. Indeed, oxidative stress leads to abnormalities by the production of ROS and RNS. The mechanism of endometriosis genesis is a complicated process that concerns the alterations in cellular immunity. Also, endometriosis is a hormonal response that illustrates stimulation in steroid hormone production. Genetic polymolymorphisms and epigenetic factors are also important in endometriosis initiation and progression. This review paper presents the role of oxidative stress, reactive oxygen species (ROS), and antioxidants and inflammatory, genetic, and epigenetic factors involved in the initiation and progression of the endometriosis. [ABSTRACT FROM AUTHOR]

It is well accepted that influenza A virus predisposes individuals to often more severe superinfections with Streptococcus pneumonia. However, the mechanisms that lead to this synergy are not clearly understood. Recent data suggests that competent Th17 immunity is crucial to clearance and protection from invasive pneumococcal disease of the lung. We demonstrate that early influenza infection significantly reduced levels of pneumococcus driven IL-12p70, IL-23 and IL-27 in human monocytes with significant impairment of IL-17A and IFN-γ in HKSP-treated allogeneic mixed lymphocyte cultures. We also provide evidence to suggest that the hemagglutinin component of the virus is at least partially responsible for this downward pressure on IL-17 responses but surprisingly this suppression occurs despite robust IL-23 levels in hemagglutinin-treated monocyte cultures. This study demonstrates that influenza can directly affect the immunological pathways that promote appropriate responses to Streptococcus pneumonia in human immune cells. Importance: Influenza virus is highly contagious and poses substantial public health problems due to its strong association with morbidity and mortality. Approximately 250,000–500,000 deaths are caused by seasonal influenza virus annually, and this figure increases during periods of pandemic infections. Most of these deaths are due to secondary bacterial pneumonia. Influenza-bacterial superinfection can result in hospitalisation and/or death of both patients with pre-existing lung disease or previously healthy individuals. The importance of our research is in determining that influenza and its component haemagglutinin has a direct effect on the classic pneumococcus induced pathways to IL-17A in our human ex vivo model. Our understanding of the mechanism which leaves people exposed to influenza infection during superinfection remain unresolved. This paper demonstrates that early infection of monocytes inhibits an arm of immunity crucial to bacterial clearance. Understanding this mechanism may provide alternative interventions in the case of superinfection with antimicrobial resistant strains of bacteria. [ABSTRACT FROM AUTHOR]

Highlights • Dendritic cells with overexpression of SOCS1 are constructed with lentivirus encoding SOCS1. • SOCS1 could block maturation process of Dendritic cells through inhibition of JAK/STAT pathway signaling. • Dendritic cells with increased expression of SOCS1 could ameliorate LPS/D-GalN induced acute liver failure. Abstract Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/ d -galactosamine induced acute liver failure via inhibition of TLR4 pathway. [ABSTRACT FROM AUTHOR]

Leishmania (L.) tropica is a causative agent of cutaneous and occasionally visceral or viscerotropic leishmaniasis in humans. The dose of parasites influences the course and outcome of disease in some Leishmania species. The effect of parasite dose on L. tropica infection in an experimental model was studied in the current paper. High and low doses of L. tropica were used for ear infection of BALB/c mice and lesion development, parasite load, and cytokine responses were assessed. L. major infection was used for comparison. Pre-infected mice were challenged in the footpad by a fixed high dose of L. tropica, and immune response and protection level were evaluated. High dose L. tropica infection in comparison to low dose results in higher lesion diameters, higher load of parasite in draining lymph node, higher levels of interferon-γ and interleukin-10, dissemination of parasite to spleen, and induction of protection against further L. tropica challenge. Comparison of L. tropica with L. major showed that L. tropica results in lower lesion diameters, more potential for growth in lymph nodes at early phases of infection, parasite dissemination to spleen, lower levels of IL-10, and a permanent lower cytokine response against low parasite dose in comparison to high dose. Our findings suggest that for L. tropica infection, only the high dose results in visceralization of the parasite and protection against further challenge of L. tropica. Therefore, the parasite dose may be an important factor in pathogenesis and immunity in L. tropica infection. [ABSTRACT FROM AUTHOR]

Abstract Numerous reports on the interactions between the immune and endocrine systems, especially growth hormone axis, can be found in the literature. Growth hormone acts mainly indirectly through insulin-like growth factor-1, which stimulates the growth and development processes, metabolism of lipids, proteins, and carbohydrates, and it also has a modulating effect on the cells of the immune system. Several studies have been conducted on the influence of growth hormone therapy on the immunological parameters in children and adults with and without growth hormone deficiency. However, there have been no definite results and some of them have been even contradictory. Some studies have suggested that administration of growth hormone increases the production of tumor necrosis factor and certain pro- and anti-inflammatory cytokines; whereas other studies have demonstrated the lack of correlation between growth hormone and interleukins. The aim of this paper was to evaluate the available literature on the interaction between growth hormone and TNF-α, pro-inflammatory (IL-1β, IL-2, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is an increasing major public health problem worldwide. The number of CKD patients on hemodialysis is growing rapidly as well. Acupuncture technique is one of the traditional Chinese medicine methods and has been used in a variety of diseases. Nowadays, the clinical application of acupuncture technique for CKD patients has become the focus for its effectiveness and security. In this paper, we will review the therapeutic effects and mechanisms of different acupuncture techniques for CKD patients. In patients with CKD, acupuncture improves renal function, reduces proteinuria, controls hypertension, corrects anemia, relieves pain, and controls many hemodialysis-related complications such as uremic pruritus, insomnia and fatigue. The mechanisms are related to the regulation of sympathetic nerve and the activation of bioactive chemicals. In conclusion, acupuncture is proved to be beneficial for CKD patients. More research, however, is needed to verify the potential mechanisms. [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]

Acute respiratory virus infection (ARI) induces CD8+ T cells with diminished cytokine production and functional impairment. The role of cellular mediators of immune impairment, specifically CD4+ regulatory T cells (Tregs), is incompletely understood in ARI. Tregs are known suppressors of effector T cell function, but whether they are detrimental or beneficial in ARI remains controversial. We show in this paper that Treg depletion leads to increased CD8+ T cell function and lower virus titer in mice infected with human metapneumovirus. We further demonstrate that Tregs play a temporal role in the immune response to human metapneumovirus and influenza: Treg depletion before infection pathologically reduces virus-specific CD8+ T cell numbers and delays virus clearance, whereas depletion 2 d postinoculation enhances CD8+ T cell functionality without reducing virus-specific CD8+ T cell numbers. Mechanistically, Treg depletion during immune priming led to impaired dendritic cell and CD8+ T cell migration. Further, early Treg depletion was associated with immune skewing toward a type 2 phenotype characterized by increased type 2 innate lymphoid cells and TH2 CD4+ T cells, which was not observed when Treg depletion was delayed until after inoculation. These results indicate that the presence of Tregs at inoculation is critical for efficient priming of the CD8+ T cell response to ARI, whereas later in infection, Tregs are dispensable for virus clearance. [ABSTRACT FROM AUTHOR]

Muscle injury occurs due to trauma, strenuous exercise or sports activities; most people affected are athletes. Ineffectively treated muscle injury can negatively affect sports careers and quality of life after retirement from sports. Reports have indicated that the current therapeutic management of muscle injury, particularly anti-inflammatory drugs, are not necessarily effective. Therefore, better therapies are required. Accumulating evidence has demonstrated melatonin's potent antioxidant and anti-inflammatory actions against muscle pathology in sarcopenia or atrophy in systemic disease. However, the underlying mechanisms for the protective effect of melatonin in the context of trauma/strenuous exercise are multifactorial and not well described. This paper reviews data on melatonin's impact on muscle injury and findings that points toward the mechanisms through which melatonin achieves muscle protection. The general concept described in this review is that melatonin inhibits NFκB, reduces cytokine expression, increases Akt that downregulates the ratio of MAFBX and MURF-1 in order to limit the extent of muscle injury and promote muscle recovery post-injury. The work discussed in this review supports the notion that melatonin may be considered a possible therapy against trauma/ sports related muscle injury. Inclusion of melatonin as a therapy in sports medicine could therefore provide a better treatment option for injured athletes and sports individuals. [ABSTRACT FROM AUTHOR]

There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS related-terms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality. 38 papers met the inclusionary criteria. The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of transforming growth factor-beta (TGF-β) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines. Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-β concentrations. The finding of elevated TGF-β concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue. [ABSTRACT FROM AUTHOR]

The article presents information on abstracts related to neoplasia. An abstract informs that ZD6474 significantly reduces polyp burden in a mouse model of intestinal cancer. ZD6474, an orally active inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor (EGFR) tyrosine kinase activity, was used to study the effect of blocking angiogenesis and EGFR signalling in multiple intestinal neoplasia mice. These mice develop numerous benign polyps due to a mutation of the adenomatous polyposis coli gene, as in familial adenomatous polyposis in humans.

For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper. [ABSTRACT FROM AUTHOR]

It is known that some iodine-containing drugs have pleiotropic effects on the body's immune response. The immune system can both inhibit and activate the production of pro-inflammatory and antiinflammatory cytokines in response to stimuli. Those properties can be valuable when developing drugs for various purposes as well as for evaluating their safety. Key regulatory cytokines that can be involved in the response to iodine are IL-4 and IFN-γ. Therefore, relation of those cytokines is often regarded as a marker when evaluating cellular and humoral immunity, including allergies. Studies of an allergic response to iodine give conflicting results. Difficulties in interpreting results are usually associated with the fact that molecular iodine is not able to cause an allergic reaction on its own. However, by acting as a hapten, iodine is capable of forming bounds with the body's proteins and consequently can induce immune response to iodinated proteins. Thus, by studying production of IL-4 and IFN-γ we can characterize effects of new iodine coordination compound on some components of the immunity. This paper presents the results of our study, where we evaluated cytotoxicity and the ability to induce production of IL-4 and IFN-γ cytokines by MDCK (Madin-Darby canine kidney cells) and PBMN (mononuclear cells from peripheral blood) after treatment with a new coordinated compound (KC). KC is a drug that contains a multiple polymer complex comprising of molecular iodine coordinated by lithium and potassium halides, di- and tri-peptides and α-dextrin. An induction of IFN-γ was only detected in PBMN cells treated at concentrations close to 50% cytotoxic concentration (CC50), which can be interpreted as a cytotoxic effect. In vivo study showed the absence of irritating effect on the skin of tested animals. Treatment had no impact on the body weight of rabbits. Results of this study add new knowledge to the influence of iodine complexes on immunity. [ABSTRACT FROM AUTHOR]

The definition of recurrent implantation failure (RIF) usually refers to failure to achieve a clinical pregnancy after going through at least three fresh/frozen cycles or transfer of at least four good-quality embryos in a woman under the age of 40 years. Embryo implantation is a complex process of the recognition and fusion between mater and fetus. On one hand, embryonic trophoblasts can express embryonic antigen and secrete cytokines in order to escape the attack of maternal immune system. On the other hand, the specialized immune cells of maternal decidua are enriched to develop a unique immune microenvironment at maternal-fetal interface. Both of them are beneficial for embryo implantation. Any immunologic disorder of the maternal -fetal interface during implantation may lead to implantation failure. With the development of reproductive immunology, the role of immune factors in the establishment of endometrial receptivity has been paid more and more attention, and the use of immunomodulators to improve the pregnancy outcome of RIF has been reported. In this paper, we described the recent research progress in immunological etiology of RIF and the related therapy. [ABSTRACT FROM AUTHOR]

Background Recently, much attention has been devoted to the possible alterations of the immune system in obsessive-compulsive disorder (OCD). Therefore, the aim of this paper was to review the current literature on the relationships between OCD and immune system. Methods A PubMed and Google Scholar search was performed with specific keywords. Results In the childhood, much emphasis has been given to the relationship between group A Streptococcus (GAS) infection and the development of a group of clinical syndromes characterized by neuropsychiatric symptoms known as “pediatric autoimmune neuropsychiatric disorders associated with streptococcus” (PANDAS). However, more recently, PANDAS has been reconsidered and evolved towards pediatric acute-onset neuropsychiatric syndrome (PANS) and/or Childhood Acute Neuropsychiatric Syndrome (CANS) all characterized by the presence of typical of OCD symptoms and tics. In adult OCD patients, different immunological parameters have been described to differ from those of healthy control subjects, although a few numbers of studies were carred out and most of them performed in small samples. Conclusions Although the exact relationships between OCD and immune processes are still unclear, available literature supports their role in the pathophysiology of OCD, while providing a fascinating hint for possible immunotherapeutic treatments in OCD. [ABSTRACT FROM AUTHOR]

3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment. In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing. [ABSTRACT FROM AUTHOR]

Triticum vulgare has been extensively used in traditional medicine thanks to its properties of accelerating tissue repair. The specific extract of Triticum vulgare manufactured by Farmaceutici Damor (TVE-DAMOR) is already present in some pharmaceutical formulations used in the treatment of decubitus ulcers, skin lesions and burns. It has been recently suggested that this Triticum vulgare extract may possess potential anti-inflammatory properties. In the light of these premises the aim of the present paper was to verify the anti-inflammatory role of TVE, using the LPS-stimulated microglia model of inflammation. In particular the effect of different concentrations of TVE on the release of several mediators of inflammation such as nitric oxide, IL-6, PGE2 and TNF alpha was evaluated. More important, the anti-inflammatory effect of TVE was confirmed also in primary rat microglia cultures. The results of the present study show that TVE exerts anti-inflammatory properties since it reduces the release of all the evaluated markers of inflammation, such as NO, IL6, TNF alpha and PGE2 in LPS-activated BV2 microglial cells. Intriguingly, TVE reduced microglia activation and NO release also in primary microglia. Indeed, to verify the pathway of modulation of the inflammatory markers reported above, we found that TVE restores the cytoplasmic expression of p65 protein, kwown as specific marker associated with activation of inflammatory response. The evidence for an inhibitory activity on inflammation of this specific extract of Triticum vulgare may open the way to the possibility of a therapeutical use of the Triticum vulgare extract as an anti-inflammatory compound in certain pathological states such as burns, decubitus ulcers, folliculitis and inflammation of peripheral nerve. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the effect of glabridin (Glab) on psoriasis. We observed that Glab significantly suppressed the levels of nitric oxide (NO), NF-κB subunit p65, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated HaCaT cells. In addition, Glab treatment reduced the expression of IL-17A, IL-22, and IL-23 in TNF- α- stimulated-HaCaT cells. These findings prompted us to test whether Glab could be used to treat psoriasis in vivo. The effects of Glab on PASI scores, histopathological changes, oxidative/anti-oxidative indexes and pro-inflammatory cytokines in IMQ-induced mice were investigated. The results indicated that Glab could reduce the PASI scores and ameliorate the deteriorating histopathology. Interestingly, RT-PCR revealed that Glab significantly decreased the mRNA expression of p65, IL-6, IL-1β, IL-17A, IL-22, and IL-23. These results were confirmed by Western blot analysis and immunohistochemistry staining. In conclusion, our present study revealed that Glab had beneficial effects on psoriasis, and the underlying mechanism may be associated with the downregulation of pro-inflammatory cytokines and the improvement of antioxidant status. Hence, Glab is a promising candidate molecule for development of effective psoriasis therapies. [ABSTRACT FROM AUTHOR]

Spores and fungal fragments found in indoor and outdoor environments originate from opportunistic fungi and they can contribute to inflammatory responses, causing a broad range of symptoms. Papers were selected and reviewed with an emphasis on the molecular mechanisms involved in the effect of fungi on immune cells, especially mast cells (MCs). Fungi can bind to antibodies and complement them, allowing them to be recognized by cells of the innate immune system, including macrophages, dendritic cells, and MCs, which are then stimulated via Toll-like receptor signaling. Fungi can cause diseases mediated by MCs and aggravate allergic inflammation. Immunosuppressed subjects can be particularly susceptible to developing diseases caused by opportunistic fungi. Mold also liberates mycotoxins that could be on volatile spores and stimulate MCs to secrete pro-inflammatory cytokines/chemokines, but this mechanism is not known. Fungi can activate the immune system directly or through mycotoxins, leading to stimulation of immune cells and chronic neuroinflammatory symptoms. Some of these processes may be inhibited by the new anti-inflammatory cytokine interleukin 37. [ABSTRACT FROM AUTHOR]

The proinflammatory cytokine interleukin-1β (IL-1β) is produced as inactive proIL-1β and then processed by caspase-1 to become active. In 2002, it was demonstrated that the intracellular multiprotein complex known as the inflammasome functions as a molecular platform to trigger activation of caspase-1. Inflammasomes are known to function as intracellular sensors for a broad spectrum of various pathogen-associated and damage-associated molecular patterns. In 1985, it was demonstrated that Porphyromonas gingivalis, a representative bacterium causing chronic periodontitis, induces IL-1 production by murine peritoneal macrophages. Since then, many studies have suggested that IL-1, particularly IL-1β plays key roles in the pathogenesis of periodontal diseases. However, the term "inflammasome" was not used until the involvement of inflammasomes in periodontal disease was suggested in 2009. Several subsequent studies on the roles of the inflammasome in the pathogenesis of periodontal diseases have been published. Interestingly, two contradictory reports on the modulation of inflammasomes by P. gingivalis have been published. Some papers have described how P. gingivalis activates the inflammasome to produce IL-1β whereas some stated that P. gingivalis inhibits inflammasome activation to subvert immune responses. Several lines of evidence have suggested that the inflammasome activation is modulated by periodontopathic bacteria other than P. gingivalis. Hence, studies on the roles of inflammasomes in the pathogenesis of periodontal diseases began only 8 years ago and many pathological roles of inflammasomes remain to be clarified. [ABSTRACT FROM AUTHOR]

Titanium (Ti) and Ti-6 Aluminium-4 Vanadium alloys are the most common materials in implants composition but β type alloys are promising biomaterials because they present better mechanical properties. Besides the composition of biomaterial, many factors influence the performance of the biomaterial. For example, porous surface may modify the functional cellular response and accelerate osseointegration. This paper presents in vitro and in vivo evaluations of powder metallurgy-processed porous samples composed by different titanium alloys and pure Ti, aiming to show their potential for biomedical applications. The porous surfaces samples were produced with different designs to in vitro and in vivo tests. Samples were characterized with scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and elastic modulus analyses. Osteogenic cells from newborn rat calvaria were plated on discs of different materials: G1—commercially pure Ti group (CpTi); G2—Ti-6Al-4V alloy; G3—Ti-13 Niobium-13 Zirconium alloy; G4—Ti-35 Niobium alloy; G5—Ti-35 Niobium-7 Zirconium-5 Tantalum alloy. Cell adhesion and viability, total protein content, alkaline phosphatase activity, mineralization nodules and gene expression (alkaline phosphatase, Runx-2, osteocalcin and osteopontin) were assessed. After 2 and 4 weeks of implantation in rabbit tibia, bone ingrowth was analyzed using micro-computed tomography (μCT). EDS analysis confirmed the material production of each group. Metallographic and SEM analysis revealed interconnected pores, with mean pore size of 99,5μm and mean porosity of 42%, without significant difference among the groups (p>0.05). The elastic modulus values did not exhibit difference among the groups (p>0.05). Experimental alloys demonstrated better results than CpTi and Ti-6Al-4V, in gene expression and cytokines analysis, especially in early experimental periods. In conclusion, our data suggests that the experimental alloys can be used for biomedical application since they contributed to excellent cellular behavior and osseointegration besides presenting lower elastic modulus. [ABSTRACT FROM AUTHOR]

Inflammation is the first biological response of the immune system to infection, injury or irritation. Evidence suggests that the anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ as well as noncytokine mediator, prostaglandin E2. Fruits, vegetables, and food legumes contain high levels of phytochemicals that show anti-inflammatory effect, but their mechanisms of actions have not been completely identified. The aim of this paper was to summarize the recent investigations and findings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables, and food legumes. Specific cytokines released for specific type of physiological event might shed some light on the specific use of each source of phytochemicals that can benefit to counter the inflammatory response. As natural modulators of proinflammatory gene expressions, phytochemical from fruits, vegetables, and food legumes could be incorporated into novel bioactive anti-inflammatory formulations of various nutraceuticals and pharmaceuticals. Finally, these phytochemicals are discussed as the natural promotion strategy for the improvement of human health status. The phenolics and triterpenoids in fruits and vegetables showed higher anti-inflammatory activity than other compounds. In food legumes, lectins and peptides had anti-inflammatory activity in most cases. However, there are lack of human study data on the anti-inflammatory activity of phytochemicals from fruits, vegetables, and food legumes. [ABSTRACT FROM AUTHOR]

Skeletal muscle tissue retains a remarkable regenerative capacity due to the activation of resident stem cells that in pathological conditions or after tissue damage proliferate and commit themselves into myoblasts. These immature myogenic cells undergo differentiation to generate new myofibers or repair the injured ones, giving a strong contribution to muscle regeneration. Cytokines and growth factors, potently released after tissue injury by leukocytes and macrophages, are not only responsible of the induction of the initial inflammatory response, but can also affect skeletal muscle regeneration. Growth factors exploit sphingosine kinase (SK), the enzyme that catalyzes the production of sphingosine 1-phosphate (S1P), to exert their biological effects in skeletal muscle. In this paper we show for the first time that bradykinin (BK), the leading member of kinin/kallikrein system, is able to induce myogenic differentiation in C2C12 myoblasts. Moreover, evidence is provided that SK1, the specific S1P-transporter spinster homolog 2 (Spns2) and S1P 2 receptor are involved in the action exerted by BK, since pharmacological inhibition/antagonism or specific down-regulation significantly alter BK-induced myogenic differentiation. Moreover, the molecular mechanism initiated by BK involves a rapid translocation of SK1 to plasma membrane, analyzed by time-lapse immunofluorescence analysis. The present study highlights the role of SK1/Spns2/S1P receptor 2 signaling axis in BK-induced myogenic differentiation, thus confirming the crucial involvement of this pathway in skeletal muscle cell biology. [ABSTRACT FROM AUTHOR]

ABSTRACT: Diet and immunity are both highly complex processes through which organisms interact with their environment and adapt to variable conditions. Parents that are able to transmit information to their offspring about prevailing environmental conditions have a selective advantage by ‘priming’ the physiology of their offspring. We used a meta‐analytic approach to test the effect of parental diet on offspring immune responses. Using the geometric framework for nutrition (a method for analysing diet compositions wherein food nutrient components are expressed as axes in a Cartesian coordinate space) to define dietary manipulations in terms of their energy and macronutrient compositions, we compiled the results of 226 experiments from 38 published papers on the intergenerational effects of diet on immunity, across a range of study species and immunological responses. We observed intergenerational impacts of parental nutrition on a number of offspring immunological processes, including expression of pro‐inflammatory biomarkers as well as decreases in anti‐inflammatory markers in response to certain parental diets. For example, across our data set as a whole (encompassing several types of dietary manipulation), dietary stress in parents was seen to significantly increase pro‐inflammatory cytokine levels measured in offspring (overall d = 0.575). All studies included in our analysis were from experiments in which the offspring were raised on a normal or control diet, so our findings suggest that a nutrition‐dependent immune state can be inherited, and that this immune state is maintained in the short term, despite offspring returning to an ‘optimal’ diet. We demonstrate how the geometric framework for nutrition can be used to disentangle the role that different forms of dietary manipulation can have on intergenerational immunity. For example, offspring B‐cell responses were significantly decreased when parents were raised on a range of different diets. Similarly, our approach allowed us to show that a parental diet elevated in protein (regardless of energy composition and relative to a control diet) can increase expression of inflammatory markers while decreasing B‐cell‐associated markers. By conducting a systematic review of the literature, we have identified important gaps that impair our understanding of the intergenerational effects of diet, such as a paucity of experimental studies involving increased protein and decreased energy, and a lack of studies directed at the whole‐organism consequences of these processes, such as immune resilience to infection. The results of our analyses inform our understanding of the effects of diet on physiological state across diverse biological fields, including biomedical sciences, maintenance of agricultural breed stock and conservation breeding programs, among others. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is hypothesized that levels of interleukin (IL)‐1β, IL‐6 and tumor necrosis factor (TNF)‐α are significantly higher in the peri‐implant sulcular fluid (PISF) of waterpipe‐smokers (WS) compared with never‐smokers with peri‐implantitis. Purpose: The aim of the present convenience sample case‐control study was to compare the levels of IL‐6, IL‐1β, and TNF‐α in the PISF of WS and never‐smokers with peri‐implantitis. Materials and Methods: Demographic data was collected using a questionnaire. Peri‐implant probing depth (PPD) was measured and crestal bone loss (CBL) was measured on digital bitewing radiographs. PISF samples were collected using paper strips and the collected PISF volume was determined. levels of IL‐6, IL‐1β, and TNF‐α were measured using enzyme linked immunosorbent assay. Study sample‐size was estimated and statistical analysis was performed. P values less than .05 were considered statistically significant. Results: Sixty‐six individuals (33 individuals in group‐1 and 33 in group‐2) were included. In groups 1 and 2, 41 and 44 implants, respectively were placed. The mean total PPD (P < .001) and peri‐implant CBL (P < .001) was statistically significantly higher around implants affected by peri‐implantitis in group‐1 compared with group‐2. The PISF volume (P < .05) collected and levels of IL‐1β (P < .01), IL‐6 (P < .01), and TNF‐α (P < .01) were statistically significantly higher among individuals in group‐1 compared with group‐2. Conclusion: WS with peri‐implantitis present increased expression of local proinflammatory cytokines in the PISF than never‐smokers. [ABSTRACT FROM AUTHOR]

Background: Although there has been abundant research on chronic low-grade inflammation as a potential mechanism underlying the link between mood disorders and cardiovascular risk, less is known about the role of inflammatory factors and anxiety disorders. The aim of this paper is to evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP) with anxiety disorders and its subgroups.Methods: The sample consisted of 3,113 participants (53.7% women; mean age: 51.0, S.D. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, S.D. 0.6). Anxiety disorders were assessed with semistructured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples.Results: After adjustment for potential confounders, current anxiety disorders (β = 0.09, 95% CI 0.00-0.17) and agoraphobia (β = 0.25, 95% CI: 0.07-0.43) at baseline were associated with a steeper increase of hsCRP levels over the follow-up period. Current posttraumatic stress disorder (PTSD) was associated with a lower increase of IL-6 levels over the follow-up period (β = -0.52, 95% CI: -1.00/-0.04). There was no evidence for an association between inflammation markers at baseline and anxiety disorders at follow-up.Conclusions: The prospective association between agoraphobia at baseline and hsCRP levels over the follow-up period suggests that chronic low-grade inflammation may be a consequence of this condition. The decrease in IL-6 in PTSD also requires further investigation. No evidence was found for chronic low-grade inflammation as a predictor of future anxiety disorders. [ABSTRACT FROM AUTHOR]

While wound therapy remains a clinical challenge in current medical practice, much effort has focused on developing biological therapeutic approaches. This paper presents a comprehensive review of delivery systems for current biologicals for the treatment of chronic wounds and severe burns. The biologicals discussed here include proteins such as growth factors and gene modifying molecules, which may be delivered to wounds free, encapsulated, or released from living systems (cells, skin grafts or skin equivalents) or biomaterials. Advances in biomaterial science and technologies have enabled the synthesis of delivery systems such as scaffolds, hydrogels and nanoparticles, designed to not only allow spatially and temporally controlled release of biologicals, but to also emulate the natural extracellular matrix microenvironment. These technologies represent an attractive field for regenerative wound therapy, by offering more personalised and effective treatments. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a global epidemic associated with increased health expenditure, and low quality of life. Many non-genetic risk factors have been suggested, but their overall epidemiological credibility has not been assessed. Methods: We searched PubMed to capture all meta-analyses and Mendelian randomization studies for risk factors of T2DM. For each association, we estimated the summary effect size, its 95% confidence and prediction interval, and the I2 metric. We examined the presence of small-study effects and excess significance bias. We assessed the epidemiological credibility through a set of predefined criteria. Results: We captured 86 eligible papers (142 associations) covering a wide range of biomarkers, medical conditions, and dietary, lifestyle, environmental and psychosocial factors. Adiposity, low hip circumference, serum biomarkers (increased level of alanine aminotransferase, gamma-glutamyl transferase, uric acid and C-reactive protein, and decreased level of adiponectin and vitamin D), an unhealthy dietary pattern (increased consumption of processed meat and sugar-sweetened beverages, decreased intake of whole grains, coffee and heme iron, and low adherence to a healthy dietary pattern), low level of education and conscientiousness, decreased physical activity, high sedentary time and duration of television watching, low alcohol drinking, smoking, air pollution, and some medical conditions (high systolic blood pressure, late menarche age, gestational diabetes, metabolic syndrome, preterm birth) presented robust evidence for increased risk of T2DM. Conclusions: A healthy lifestyle pattern could lead to decreased risk for T2DM. Future randomized clinical trials should focus on identifying efficient strategies to modify harmful daily habits and predisposing dietary patterns. [ABSTRACT FROM AUTHOR]

Background Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen reduction accompanied by the cartilage degradation. Eicosanoids are responsible for the progressive destruction of cartilage and bone, however neither steroids, nor the non steroidal anti-inflammatory drugs (NSAIDs), cannot slow down cartilage and bone destruction providing only symptomatic improvement. The current rheumatoid arthritis treatment options include mainly the use of disease-modifying anti-rheumatic drugs, the corticosteroids, the NSAIDs and biological agents. Methods PubMed, Cochrane, and Embase electronic database were used as the main sources for extracting several articles, reviews, original papers in English for further review and analysis on the implication of arachidonic acid metabolites with rheumatoid arthritis and different strategies of targeting arachidonic acid metabolites, different enzymes or receptors for improving the treatment of rheumatoid arthritis patients. Results We first focused on the role of individual prostaglandins and leukotrienes, in the inflammatory process of arthritis, concluding with an outline of the current clinical situation of rheumatoid arthritis and novel treatment strategies targeting the arachidonic acid pathway. Conclusions Extended research is necessary for the development of these novel compounds targeting the eicosanoid pathway, by increasing the levels of anti-inflammatory eicosanoids (PGD 2 ,15dPGJ 2 ), by inhibiting the production of pro-inflammatory eicosanoids (PGE 2 , LTB 4 , PGI 2 ) involved in rheumatoid arthritis or also by developing dual compounds displaying both the COX-2 inhibitor/TP antagonist activity within a single compound. [ABSTRACT FROM AUTHOR]

Malicious intruders on networks have been the major concerns since last one decade or more, to gain the focus of many researchers. Inspired from human immune system, Dendritic Cell Algorithm has already been implemented for intrusion detection systems. Dendritic cells are the sole of human immune system which are responsible for combining signals in the tissue and reporting to the immune system of any variation in the signal concentration. In this paper an intrusion detection system is proposed and implemented for KDD data set using probabilistic dendritic cell algorithm. Besides taking statistically derived input signal concentration, probabilistic measure based on Shanon's entropy are taken as input signal concentration to compute the output cytokines. Proposed method has shown significant improvement as compared to other existing techniques used in intrusion detection system. [ABSTRACT FROM AUTHOR]

Caspase-1-mediated pyroptosis is the predominance for driving CD4+ T cells death. Dying infected CD4+ T cells can release inflammatory signals which attract more uninfected CD4+ T cells to die. This paper is devoted to developing a diffusive mathematical model which can make useful contributions to understanding caspase-1-mediated pyroptosis by inflammatory cytokines IL-1β released from infected cells in the within-host environment. The well-posedness of solutions, basic reproduction number, threshold dynamics are investigated for spatially heterogeneous infection. Travelling wave solutions for spatially homogeneous infection are studied. Numerical computations reveal that the spatially heterogeneous infection can make R0>1, that is, it can induce the persistence of virus compared to the spatially homogeneous infection. We also find that the random movements of virus have no effect on basic reproduction number for the spatially homogeneous model, while it may result in less infection risk for the spatially heterogeneous model, under some suitable parameters. Further, the death of infected CD4+ cells which are caused by pyroptosis can make R0<1, that is, it can induce the extinction of virus, regardless of whether or not the parameters are spatially dependent. [ABSTRACT FROM AUTHOR]

Due to its strong proliferation-reducing effects on keratinocytes, and also anti-inflammatory properties, the isoflavone genistein has already been proposed as a possible antipsoriatic compound. As there is still no detailed information on this topic, we examined the effects of genistein by using an in vitro model of both, normal and “psoriasis-like” keratinocytes at this stage of our work exhaustively testing the selected flavonoid in a mono-treated experimental design. Gene expression studies revealed transcriptional changes that confirms known disease-associated pathways and highlights many psoriasis-related genes. Our results suggested that aberrant expression of genes contributing to the progress of psoriasis could be improved by the action of genistein. Genistein prevented “cytokine mix” as well as TNF-α-induced NF-κB nuclear translocation, with no effect on the PI3K signaling cascade, indicating the luck of turning this pathway into NF-κB activation. It could have attenuated TNF-α and LPS-induced inflammatory responses by suppressing ROS activation. Regardless of the type of keratinocyte stimulation used, reduction of cytokine IL-8, IL-20 and CCL2 production (both at RNA and protein level) following genistein treatment was visible. Because investigations of other groups supported our commentary on potential administration of genistein as a potential weapon in the armamentarium against psoriasis, it is believed that this paper should serve to encourage researchers to conduct further studies on this subject. [ABSTRACT FROM AUTHOR]

Quantitative and dynamic analyses of immune cell secretory cytokines are essential for precise determination and characterization of the “immune phenotype” of patients for clinical diagnosis and treatment of immune-related diseases. Although multiple methods including the enzyme-linked immunosorbent assay (ELISA) have been applied for cytokine detection, such measurements remain very challenging in real-time, high-throughput, and high-sensitivity immune cell analysis. In this paper, we report a highly integrated microfluidic device that allows for on-chip isolation, culture, and stimulation, as well as sensitive and dynamic cytokine profiling of immune cells. Such a microfluidic sensing chip is integrated with cytometric fluorescent microbeads for real-time and multiplexed monitoring of immune cell cytokine secretion dynamics, consuming a relatively small extracted sample volume (160 nl) without interrupting the immune cell culture. Furthermore, it is integrated with a Taylor dispersion-based mixing unit in each detection chamber that shortens the immunoassay period down to less than 30 minutes. We demonstrate the profiling of multiple pro-inflammatory cytokine secretions (e.g. interleukin-6, interleukin-8, and tumor necrosis factors) of human peripheral blood mononuclear cells (PBMCs) with a sensitivity of 20 pg ml−1 and a sample volume of 160 nl per detection. Further applications of this automated, rapid, and high-throughput microfluidic immunophenotyping platform can help unleash the mechanisms of systemic immune responses, and enable efficient assessments of the pathologic immune status for clinical diagnosis and immune therapy. [ABSTRACT FROM AUTHOR]

Sepsis, a systemic inflammation as a response to a bacterial infection, is a huge unmet medical need. Data accumulated over the last decade suggest that the nutritional status of patients as well as composition of their gut microbiome, are strongly linked with the risk to develop sepsis, the severity of the disease and prognosis. In particular, the essential micronutrient zinc is essential in the resistance against sepsis and has shown to be protective in animal models as well as in human patients. The potential mechanisms by which zinc protects in sepsis are discussed in this review paper: we will focus on the inflammatory response, chemotaxis, phagocytosis, immune response, oxidative stress and modulation of the microbiome. A full understanding of the mechanism of action of zinc may open new preventive and therapeutic interventions in sepsis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic, recurrent inflammatory skin disease, which is frequently familial. The main cause of the disease seems to be a defect of the epidermal barrier resulting from a genetic predisposition concerning the epidermis, functioning of the immune system as well as environmental factors (which are not related to the immune system). Genes responsible for encoding protein S100, filaggrin, proteases and their inhibitors are the main genes related to the problem of epidermal barrier dysfunction. There is a close connection between structural and immunological processes. Increased expression of cytokine Th2 profile belongs to the latter category. The objective of the present paper is to describe the influence of aforementioned factors on epidermis structure and dysfunction which leads to clinical symptoms of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Biomaterial surface topography plays a vital role in the osteointegration of implants by regulating the early cell responses and tissue growth-in. However, most of the previous researches focused on the effects of osteogenic cells, only a little is known about the immune cells which dominate osteogenesis after implanting. In this paper, patterned titanium coatings were fabricated and the effects of surface topography on the macrophage behaviors were investigated. On patterned titanium surface, macrophages preferred to polarize to M2, while macrophages on traditional titanium coatings presented higher M1 polarization. Nearly 70% higher expression of anti-inflammatory genes, including interleukin-4, interleukin-10, interleukin-1ra, and arginase, were detected on the patterned titanium coatings. While the pro-inflammatory genes, such as interleukin-1β, interleukin-6, tumor necrosis factor-α, interferon-γ, and inducible nitric oxide synthase were notably depressed. Up-regulation of the osteoinductive cytokines were also detected on the patterned coatings, which indicated advantageous osteogenic microenvironment provided by macrophages. Immunomodulation effect on osteogenesis was also investigated in this study. Stimulated with RAW cells/patterned coatings conditioned medium, bone marrow stem cells presented nearly 1.5 fold higher expression of osteogenic genes and more mineralization nodules than the traditional sprayed Ti coatings. All these results suggested that modulating materials with a patterned surface might be a valuable strategy to endow the implants with favorable osteoimmunomodulatory properties. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to examine the relationship between bracket design and ratio of five proinflammatory cytokine, in gingival crevicular fluid (GCF), and bacterial adhesion without tooth movement influence. Design The sample was comprised of 20 participants, aged 11 to 15 years old (mean age: 13.3 years ± 1.03). A conventional Gemini™ metallic bracket and two self-ligating brackets, In-Ovation ® R and SmartClip™, were bonded to the maxillary incisors and canines. GCF was collected using a standard filter paper strip before and 60 days after bonding. The cytokine levels (IL-12, IL-1α, IL-1β, IL-6 and TNF-α) were performed by the LUMINEX assay. The levels of the red and orange bacterial complexes were analyzed by the Checkerboard DNA-DNA hybridization. The data of cytokine and bacterial complexes were carried out using the non-parametric tests at 5% of significance level. Results Increased cytokine levels were observed. However, only the SmartClip™ group showed a significantly increased level of TNF-α (p = 0.046). The SmartClip™ brackets group presented higher levels of red complex bacteria. Conclusions The bracket design affected cytokine levels and bacterial adhesion since it was observed that the proinflammatory cytokines released in GCF to the SmartClip™ group showed an increase in the TNF-α levels associated with higher bacterial levels, which possibly represents greater inflammatory potential. Thereby, the bracket design should be considered in patients with risk of periodontal disease and root resorption. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic, recurrent inflammatory skin disease, which is frequently familial. The main cause of the disease seems to be a defect of the epidermal barrier resulting from a genetic predisposition concerning the epidermis, functioning of the immune system as well as environmental factors (which are not related to the immune system). Genes responsible for encoding protein S100, filaggrin, proteases and their inhibitors are the main genes related to the problem of epidermal barrier dysfunction. There is a close connection between structural and immunological processes. Increased expression of cytokine Th2 profile belongs to the latter category. The objective of the present paper is to describe the influence of aforementioned factors on epidermis structure and dysfunction which leads to clinical symptoms of atopic dermatitis. [ABSTRACT FROM AUTHOR]

In animals and humans, immune system performs an important function to maintain the constancy of the body internal environment, carried out by recognizing and eliminating alien substances of antigenic nature from the body. This immune system function is carried out with the congenital and acquired immunity factors. Different types of radiation, heavy metal salts, vitamin and micronutrient deficiency, stressful situations, age-related changes in the lympho-myeloid complex, therapy with anti-tuberculosis, antibacterial, hormonal, cytostatic drugs and a number of other factors lead to the development of immune diseases. These diseases can be treated with a set of immunotherapy methods; use of immunostimulants is one of them. Today, immunostimulants are distinguished as of microbial, thymic, bone marrow, cytokine, nucleic, plant and synthetic origin. Azaheterocyclic compounds comprise a class of compounds that have demonstrated significant biological activities against various human diseases. We suggest that azaheterocyclic compounds with a piperidine nucleus are perspective for the search for new effective immunostimulating drugs. To study their immunostimulating activity, the following compounds were taken: BIV-3 - 1-(3-butoxypropyl)-3-methylpiperidine 4-spiro 5'-imidazolidine-2',4'- dione, BIV-4 - 1-(2-ethoxyethyl)-4-hydroxy-4-dimethoxyphosphorylpiperidine, BIV-7 - complex of 3-(2-morpholinoethyl)-7-(3-isopropoxypropyl)-3,7-diazabicyclo [3.3.1] nonane with β-cyclodextrin. The comparison drug was methyluracil. Results of the studies are presented in this paper. [ABSTRACT FROM AUTHOR]