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Improved spectroscopy system for detecting small blood components. The improved spectral detection system, which can improve the prediction accuracy of small blood components. The graph expresses that when we only have spectral data, we can use model 1 to predict the concentration of non-target components to obtain the predicted value of the concentration of non-target components, so as to find the interval of the spectrum, and then predict the target components to obtain the predicted concentration value. The purpose of two model predictions on spectral data is to improve the accuracy of predicting small blood components. [Display omitted] • In this paper, a system is designed to improve the detection of small blood components by dynamic spectroscopy. • This paper provides a new idea for the spectral analysis of blood. • A partition modeling method considering multiple non-target components is proposed. In the realm of biomedical engineering, improving the prediction accuracy of noninvasive detection of small blood components using spectroscopic approaches has been a challenge. Because blood contains numerous complex components, according to the impact of the M factor in the "M+N" theory, the concentration of non-target components affects the accuracy of spectral detection of target components. This paper investigates an improved system for the noninvasive detection of small blood components based on dynamic spectroscopy and the "M+N" theory. After screening the data quality of the samples collected using dynamic spectroscopy, the remaining 377 samples are subjected to full modeling to determine their predicted concentrations, according to the concentrations of various non-target components like hemoglobin, red blood cells, and platelets. Following that, a complete system for the noninvasive detection of small blood components is constructed by dividing suitable intervals based on non-target components' predictive values, performing partial least squares (PLS) modeling with lymphocytes as the target component within each interval, and combining them with wavelength screening to improve the target component's predictive accuracy. When compared to the conventional technique, the correlation coefficient of the prediction set (Rp) increased by about 57.7 %, and the root mean square error (RMSEP) decreased by about 76.8 %. It has been demonstrated that the system can considerably increase the small blood components' predicted accuracy of the spectrum analysis, as well as present an idea for solving the problem of spectral detection of small blood components. [ABSTRACT FROM AUTHOR]

Graphical abstract Image 1 Abstract Recent advances in the development of protein-based vaccines have expanded the opportunities for preventing and treating both infectious diseases as well as cancer. However, the development of readily and efficient antigen delivery systems capable of stimulating strong cytotoxic T-lymphocyte (CTL) responses remains a challenge. With the attempt to closely mimic the properties of viruses in terms of their size and molecular organization, we constructed RNA (which is a ligand for Toll-like receptor 7 (TLR7) and TLR8) and antigen-loaded nanoparticles resembling the structural organization of viruses. Cationic polymers containing either azide or bicyclo[6.1.0]nonyne (BCN) groups were synthesized as electrostatic glue that binds negatively charged single stranded RNA (PolyU) to form a self-crosslinked polyplex core. An azide-modified model antigen (ovalbumin, OVA) and a BCN-modified mannosylated or galactosylated polymer were sequentially conjugated to the RNA core via disulfide bonds using copper free click chemistry to form the shell of the polyplexes. The generated reducible virus mimicking particles (VMPs) with a diameter of 200 nm and negatively surface charge (−14 mV) were colloidally stable in physiological conditions. The immunogenicity of these VMP vaccines was evaluated both in vitro and in vivo. The surface mannosylated VMPs (VMP-Man) showed 5 times higher cellular uptake by bone marrow derived DCs (BMDCs) compared to galactosylated VMP (VMP-Gal) counterpart. Moreover, VMP-Man efficiently activated DCs and greatly facilitated MHC I Ag presentation in vitro. Vaccination of mice with VMP-Man elicited strong OVA-specific CTL responses as well as humoral immune responses. These results demonstrate that the modular core-shell polymeric nanoparticles described in this paper are superior in inducing strong and durable immune responses compared to adjuvanted protein subunit vaccines and offer therefore a flexible platform for personalized vaccines. Highlights • Stable virus-structure mimicking particles (VMPs) with PolyU RNA core and antigen protein shell can be modularly fabricated by exploiting copper free click chemistry. • VMPs with poly(mannose) modification (VMP-Man) efficiently target and activate dendritic cells. • Mice immunized with VMP-Man showed superior antibody and cytolytic T cell responses. [ABSTRACT FROM AUTHOR]

Highlights • Transfer learning approaches are employed to build a complete identification system for white blood cells (WBCs) in blood smear image. • A complete end-to-end CNN architecture is proposed to identify the different WBCs types (basophil, eosinophil, lymphocyte, monocyte and neutrophil). • The proposed CNN architecture (WBCsNet) is the first deep learning architecture for WBCs identification which achieved a higher classification accuracy more than the traditional WBCs identification systems or even the transfer learning approaches. • The proposed WBCsNet is re-employed as a pre-trained network and achieves high accuracy scores for classifying limited balanced dataset. • We present features visualization for the WBCsNet activation which reflect higher reasonable response than the pre-trained activated one. Abstract Background and objectives White blood cells (WBCs) differential counting yields valued information about human health and disease. The current developed automated cell morphology equipments perform differential count which is based on blood smear image analysis. Previous identification systems for WBCs consist of successive dependent stages; pre-processing, segmentation, feature extraction, feature selection, and classification. There is a real need to employ deep learning methodologies so that the performance of previous WBCs identification systems can be increased. Classifying small limited datasets through deep learning systems is a major challenge and should be investigated. Methods In this paper, we propose a novel identification system for WBCs based on deep convolutional neural networks. Two methodologies based on transfer learning are followed: transfer learning based on deep activation features and fine-tuning of existed deep networks. Deep acrivation featues are extracted from several pre-trained networks and employed in a traditional identification system. Moreover, a novel end-to-end convolutional deep architecture called "WBCsNet" is proposed and built from scratch. Finally, a limited balanced WBCs dataset classification is performed through the WBCsNet as a pre-trained network. Results During our experiments, three different public WBCs datasets (2551 images) have been used which contain 5 healthy WBCs types. The overall system accuracy achieved by the proposed WBCsNet is (96.1%) which is more than different transfer learning approaches or even the previous traditional identification system. We also present features visualization for the WBCsNet activation which reflects higher response than the pre-trained activated one. Conclusion a novel WBCs identification system based on deep learning theory is proposed and a high performance WBCsNet can be employed as a pre-trained network. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Biologically and environmentally resorbable electronic devices support application possibilities that cannot be addressed with conventional technologies. This paper presents highly conductive, water-soluble composites that can be printed to form contacts, interconnects, antennas, and other important features that are essential to nearly all systems of this type. An optimized material formulation involves in situ polymerization to yield a polyanhydride containing a dispersion of molybdenum microparticles at appropriate concentrations. Comparisons of essential physical and electrical properties of these materials to those of composites formed with other polymers and other metal microparticles reveal the relevant considerations. Various functional demonstrations of screen-printed test structures and devices illustrate the suitability of these conductive inks for use in water-soluble electronic devices. A key advantage of the material introduced here compared to alternatives is its ability to maintain conductance over significant periods of time while immersed in relevant aqueous solutions. Studies involving live animal models establish the biocompatibility. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2), the core component of the polycomb group complex, plays a major role in normal hematopoiesis. The molecular function of EZH2 is to establish H3K27me3 mark on specific genes by which promotes transcriptional repression of target genes. The activity of EZH2 affects the balance between self-renewal and differentiation of hematopoietic stem cells. In addition, EZH2 contributes to the cell cycle regulation in mature lymphocytes. A large number of studies have been performed to identify the implication of EZH2 in tumor development of leukemia. Aberrant expression of EZH2 is increasingly recognized in leukemic malignancies. To clarify its therapeutic potential in hematopoietic malignancies it should be determined whether EZH2 is involved in the pathology of these neoplasms. This paper reviews the current knowledge of the role of EZH2 in the pathogenesis of myeloid and lymphoid leukemia. We will discuss the mechanisms in which microRNAs regulate the expression of EZH2 in different types of leukemias that may provide a means to alter cancer epigenetics associated to tumorogenesis to achieve therapeutic benefits. [ABSTRACT FROM AUTHOR]

Autoimmunity is a status that immune mechanisms react against self-structure. The immune mechanisms, including cellular and molecular elements have been developed to immune body against foreign invades. Multiple factors such as genetic and epigenetic background, hormonal status, microbiome, and other factors can cause launching the autoreactive responses, in which the immune tolerance breaks and immune mechanisms are against self-antigens. Apoptosis is one of the important mechanisms in maintaining the tolerance and eliminating the autoreactive lymphocyte clones. Due to survivin roles in apoptosis and proliferation, numerous researches have been paying attention to survivin expression and function in autoreactive lymphocytes and tissue cells, playing important roles in the pathogenesis of autoimmune diseases. New line of evidence has been supporting the role of survivin dysfunction or aberrant expression in deriving autoreactive lymphocytes or some important immune tissues, which may underpin the autoimmune conditions such as Lichen planus (LP), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Myasthenia gravis (MG), Multiple sclerosis (MS), Systemic sclerosis (SSc), Psoriasis, and Inflammatory bowel disease (IBD). Hence, the purpose of the current paper was to review the survivin role in the etiology and pathogenesis of abovementioned autoimmune diseases. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) is an autologous product prepared from whole blood (WB) that is widely used in regenerative medicine. In clinical practice, discontinuous centrifugation is used for both hand- and machine-prepared PRP. However, separation of WB fractions via centrifugation is a complex process, and the lack of clear mechanisms limits the understanding and evaluation of PRP preparation methods This paper focuses on the distribution, recovery and concentration factor of platelets and leukocytes in L-PRP (leukocyte and platelet-rich plasma) to define a concentration pattern for these blood components due to centrifugation conditions. WB collected from three healthy donors was centrifuged for 10 min at 50–800 xg in a first step and then at 400 xg in a second step. The results from the first centrifugation step showed most platelets to be distributed in the upper layer (UL) and the buffy coat (BC), with approximately 14.5 ± 5.2% retained in the bottom layer (BL). Most leukocytes were present in the BL. The greatest platelet recoveries from L-PRP were obtained at up to 150 xg (88.5 ± 16.9%). The cumulative concentration factors with respect to the WB from the second centrifugation step were 6 and 1.2 for platelets and leukocytes, respectively. Thus, the concentration patterns delineated three centrifugation ranges with platelet/leukocyte ratios of 205 ± 18, 325 ± 15 and 107 ± 4 and lymphocyte/granulocyte ratios of 1.54 ± 0.74, 0.90 ± 0.08 and 0.42 ± 0.07. These findings contribute to a scientifically based standardization of L-PRP preparations. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign, chronic inflammatory disease that presents alterations in immune response that can be detected in eutopic endometrium, peritoneal fluid and peripheral blood of affected women. Regulatory T (T Reg ) cells are a subpopulation of T lymphocytes specialized in immune regulation that seem to participate in the development of endometriosis, by suppressing the immune response and favoring the establishment of lesions. Our aim was to review the scientific literature that evaluates T Reg cell phenotypes in the context of endometriosis. PRISMA statement for systematic reviews was applied, using “regulatory T cells” and “endometriosis” as keywords in the following databases: PubMed, Cochrane, EMBASE and Lilacs. The initial search and abstract review yielded 41 papers relating to the subject. At the end, 12 studies, published between 2009 and 2016, were included. Most studies that analyzed T Reg cells did not characterize these cells with current Bona Fide markers. In peritoneal fluid and endometriotic lesions, there was a higher concentration of T Reg cell phenotype and/or T Reg cell expression markers in patients with endometriosis when compared with controls. However, there is still not a consensus about T Reg cells concentration in eutopic endometrium and peripheral blood between the revised studies. Taken together, this data collection suggests that endometriosis is related to T Reg cells alterations, although further studies are necessary to reach more precise conclusions, especially regarding the percentage of these cells in eutopic endometrium and peripheral blood. This systematic review attempted to provide instructive and up-to-date collection of data that may help better design future studies. [ABSTRACT FROM AUTHOR]

Gestagens are the most frequently used steroid hormones in hormone-replacement therapy in the treatment of threatened miscarriage during the first trimester of pregnancy. This therapy has been applied in a large number of women with threatened abortion, despite various degrees of success of its efficacy. Genetic factors play a key role in miscarriages, especially in the initial stages. Cytogenetic biomarkers such as micronucleus (MN) test, chromosomal aberrations (CAs), and sister chromatid exchanges (SCEs) provide information on DNA damage. Cytogenetic markers detecting DNA damage have become very popular and useful in analysing genetic risk associated with hormone-replacement therapy. Cytogenetic studies presented heterogenous information. In many in vitro studies synthetic gestagens have been shown to induce genotoxic effects, and it was evaluated using three cytogenetic biomarkers. Genotoxic effects of gestagens have also been confirmed in in vivo studies that were conducted involving patients who received gestagen therapy during pregnancy and their newborns. However, some studies have shown that hormone-replacement therapy does not have genotoxic effects. In this paper, we summarize the results from previous studies. We also describe the usefulness of these biomarkers in the detection of genotoxic effects of hormone-replacement therapy. [ABSTRACT FROM AUTHOR]

The Acquired Immune Deficiency Syndrome (AIDS) affects the life of millions of people around the world. Although rapid and low cost screening tests are widely available for the diagnosis of HIV infection, the count of CD4+ T lymphocytes remains a drawback in the areas mostly affected by the HIV, being this control imperative for assessing the deterioration of the immunological system and the progression towards AIDS, when the counting of cells falls down 200 cells μL −1 . This paper describes a high-throughput, simple and rapid method for CD4+ T lymphocytes quantification, directly in whole blood, based on a magneto ELISA. The CD4 cells are separated and preconcentrated from whole blood in magnetic particles, and labeled with an enzyme for the optical readout performed with a standard microplate reader. The magneto ELISA is able to reach the whole CD4 counting range of medical interest, being the limit of detection as low as 50 CD4+ cells per μL of whole blood, without any pretreatment. This method is a highly suitable alternative diagnostic tool for the expensive flow cytometry at the community and primary care level, providing a sensitive method but by using instrumentation widely available in low-resource settings laboratories and requiring low-maintenance, as is the case of a microplate reader operated by filters. [ABSTRACT FROM AUTHOR]

The effect of exposure to polycyclic aromatic hydrocarbons (PAHs) to induce micronuclei (MN) measured using the lymphocytes cytokinesis-block micronucleus (CBMN) assay were evaluated in 34 studies according to the exposure: 20 studies in coke oven workers, 7 studies in different occupational exposures as alluminium industry workers, rubber factory workers, road construction workers, airport workers and diesel exposed workers, 6 studies on environmentaly exposed groups as police, volunteers and children. Reviewed papers indicate that the CBMN assay is a sensitive biomarker of PAHs exposure in polluted air. Reviewed studies confirmed previous conclusions, that the frequency of MN measured using the lymphocyte CBMN is not significantly affected by smoking, females are more sensitive to PAHs than males, the frequency of MN is increased with age. [ABSTRACT FROM AUTHOR]

The koala ( Phascolarctos cinereus ) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti-koala CD4 monoclonal antibody (mAb). The koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti-CD4 mAb was used to measure the levels of CD4 + lymphocytes collected from koala spleens (41.1%, range 20–45.1%) lymph nodes (36.3%, range 19–55.9%) and peripheral blood (23.8%, range 17.3–35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the koala CD4 molecule and used in immunohistochemistry to identify CD4 + cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4 + T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4 + T cells play in protection against chlamydial infection in koalas and also enhance our knowledge of how KoRV affects the koala immune system. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (allo-SCT) is considered the cornerstone in the treatment of several malignant and not malignant hematological diseases. However, relapse of hematological disease after allo-SCT is considered the most challenging point in the field. The risk can be reduced through optimal patients, donor and disease selection before allo-SCT, but harnessing donor immune system is an appealing way to treat or avoid disease relapse. Donor lymphocyte infusion (DLI) is a simple and effective therapy after allo-SCT. In this paper, the efficacy of DLI will be analyzed in different hematological diseases, focusing also on their therapeutic or pre-emptive use. [ABSTRACT FROM AUTHOR]

Marsupials are a group of mammals that give birth to immature young lacking mature immune tissues at birth, and are unable to mount their own specific immune defence. Their immune tissues develop in a non-sterile ex-utero environment unlike that of eutherian mammals such as ourselves. Marsupials are therefore ideal models for studying the development of immune tissues, in particular haematopoiesis, yet relatively little has been investigated. Most studies have been restricted to histological or immunohistological studies, however some factors likely to be involved, based on eutherian studies in haematopoiesis, have been isolated and characterised, including a few key markers, and some cell signaling and regulation molecules, mostly involved in lymphocytopoiesis. However the role of many molecules in haematopoiesis is largely presumed. We currently lack much of the rudimentary information regarding time of appearance and expression levels of these molecules, and no functional studies have been conducted. This paper reviews our knowledge of marsupial haematopoiesis to date, and highlights the need for future research in marsupials to gain further insights into the evolution of haematopoiesis. [ABSTRACT FROM AUTHOR]

Given the fact that NF-κB stays as a dormant molecule in the cytoplasm in steady state, one common step in all the metabolic activities comprising NF-κB is its activation. Consequently there are two pathways of interest related to NF-κB activation: Canonical and alternate. Both the pathways involve ubiquitination of its repressors, that is to say ubiquitination of I-κB by NEMO/IKK-α/IKK-β complex in case of NF-κB1 and that of p100 by IKK-α homodimer in case of NF-κB2. This paper attempts to figure out the ubiquitination sites in alternate pathway of NF-κB activation using a purely computational approach. We initiated the work by acquiring the genes involved in NF kappa B alternate pathway through Agilent literature search. For this we employed the Cytoscape and STRING database. Secondly, the MSA was built using the sequences obtained through BLAST search, and the results were used to update the original sequence list, which was further refined using HMMER. Structural alignment was achieved via Modeller libraries. The final model has been refined using loop_model and asses_dope functions of Modeller. Ubiquitination site is predicted to be comprised of residues ‘SPECLDLLVDS’ between sites 178 and 188, both positions inclusive. Unlike the classical pathway, due to absence of parallel studies for p100/RelB, a quality match could not be performed, but future studies are in pipeline to replicate the methodology for NF-κB1 activation and compare the results with existing observations. The study can be used to understand the cofactors involved and ubiquitination sites employed during the activation process during drug designing activities. The methodology can be easily scaled and adapted for classical pathway as well. [ABSTRACT FROM AUTHOR]

A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches. [ABSTRACT FROM AUTHOR]

Up-regulation of glycolysis, a well recognized hallmark of cancer cells, was also found to be predictive of poor chemotherapy response. This observation suggested the attempt of sensitizing cancer cells to conventional chemotherapeutic agents by inhibiting glucose metabolism. Lactate dehydrogenase (LDH) inhibition can be a way to hinder glycolysis of cancer cells without affecting the metabolism of normal tissues, which usually does not require this enzymatic activity. In this paper, we showed that two LDH inhibitors (oxamate and galloflavin) can increase the efficacy of cisplatin in cultured Burkitt’s lymphoma (BL) cells and that this potentiating effect is not exerted in proliferating normal lymphocytes. This result was explained by the finding that in BL cells LDH inhibition induced reactive oxygen species (ROS) generation, which was not evidenced in proliferating normal lymphocytes. In BL cells treated with the association of cisplatin and LDH inhibitors, these ROS can be a further cause of DNA damage, to be added to that produced by cisplatin, leading to the failure of the response repair. At present LDH inhibitors suitable for clinical use are actively searched; our results can allow a better understanding of the potentiality of LDH as a possible target to develop innovative anticancer treatments. [ABSTRACT FROM AUTHOR]

The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. [ABSTRACT FROM AUTHOR]

Precise target distribution is a key issue for further appropriate applications of fangjis (formulas) with similar efficacy and herbal constituents to maximize efficacy and minimize toxicity. To develop an algorithm for investigating the differential target distributions and characteristic mechanisms of fangjis. In this study, we proposed a Modulome-Fangjiome Association Study (MoFAS) for comparing fangjis from qi-invigorating and xue-nourishing fangjiome (represented by four fangjis: FEJ, SDT, LYG and QOL). Firstly, the database-driven target network of these 4 fangjis was constructed as qi-xue network and decomposed into modules. Then, the modular map with functional landscape were constructed based on consistency score and enrichment analysis. Finally, we employed a targeting rate (TR) matrix to assess the contribution of this fangjiome to modulome (a set of modules) and compared characteristic effect of fangjis by principal component analysis (PCA). A qi-xue network constituted by 579 proteins and 23 modules were constructed. In the functional landscape, 3 primary modules were mainly involved in the endocrine system and environmental adaptation. For the target distribution, SDT and QOL were more similar; the FEJ and LYG were located distant from other fangjis according to PCA. The common effects of FEJ, SDT, and QOL focused on stress response and organism development in environmental perturbation, but the FEJ was superior in regulating critical targets, primarily focusing on hormone and neurotransmitter processes. SDT and QOL were concentrated on the majority scale of the qi-xue network, especially for the mitotic cell cycle and development. LYG only targeted lymphocyte costimulation and icosanoid biosynthetic processes. In this study, for the first time, we investigated the difference in the target distribution of qi-invigorating and xue-nourishing fangjiome and provided direct evidence for the characteristic therapeutic effect of these fangjis, which may promote the precise application of fangjis and support the identification of appropriate populations. [Display omitted] • This strategy provided a systematical exploration of target distribution for multiple-target and multiple-herb fangjis. • This strategy promoted precise application of fangjis from identical fangjiome and identification of appropriate populations. • This paper is a paradigm for precision medicine of fangjis and network-based drug discovery. [ABSTRACT FROM AUTHOR]

• Nisin shows a multifactorial immunomodulatory effect. • Nisin modulates cytokine response both in vitro and in vivo. • Nisin can affect various populations of immune cells. • Effects of nisin on immune cells depend on their functional state. • In the infected organism nisin shows anti-inflammatory effects. Nisin, a member of class I bacteriocins known as lantibiotics, is produced by the lactic acid bacterium Lactococcus lactis and is characterized by a wide spectrum of antibacterial activity against gram-positive bacteria. This characteristic in conjunction with its low toxicity and safety of use in food has contributed to the worldwide success of nisin as a natural food preservative. This lantibiotic has attracted interest as a potential natural therapeutic agent for the control of bacterial infections. However, similar to other antimicrobial peptides of natural origin, the spectrum of biological activity of nisin surpasses its antibacterial properties, encompassing interesting and incompletely understood immunotropic characteristics. This paper is a systematic review of the current information about the potential immunomodulatory properties of nisin based on in vitro and in vivo studies in various experimental models. We also discuss the effect of potentially probiotic, nisin-producing L. lactis strains on the immune system of animals. [ABSTRACT FROM AUTHOR]

Despite the conventional reputation of neutrophils to have antibacterial properties, recent studies have put emphasis and are interested in the role of neutrophils in the spread and treatment of cancer. It has been shown that the infiltration of neutrophils, either by exerting pro- or anti-tumoral effects, probably affects tumor prognosis. Tumor-associated neutrophils (TANs) probably participate in tumor promotion and development in different ways, such as increasing genomic instability, induction of immunosuppression, and increasing angiogenesis. Despite major advances in breast cancer treatment, it is the second leading cause of death in American women. It has been revealed that inflammation is a fundamental issue in the treatment of this cancer because tumor growth, invasion, metastasis, and vascularization can be affected by inflammatory factors. It is demonstrated that enhanced neutrophil to lymphocyte ratio probably contributes to the raised rate of mortality and decreased survival among breast cancer cases. The present review explores the biology of TANs, their suspected interactions in the breast cancer microenvironment, and their functions in preserving the tumor microenvironment and progression of tumors. Furthermore, their potential as therapeutic targets and clinical biomarkers has been discussed in this paper. [ABSTRACT FROM AUTHOR]

Autologous tumor infiltrating lymphocyte (TIL) therapy refers to a kind of immunotherapy in which the tumor-resident lymphocytes are harvested, cultured, and then transferred into the patient. In spite of some well-known TILs expansion recommendations, there is a lack of well-established TILs injection protocol. This paper addresses the challenge using a feedback-based control strategy. Utilizing Lyapunov technique, a novel dose calculation method is proposed which considers TILs pharmacokinetics. Then, to determine the timing of TILs administration, the concept of therapeutic window in pharmacy is exploited. The resultant therapy protocol is both practical and implementable while it ensures tumor remission. Comparing with previous studies, the proposed method takes the discontinuity of TILs delivery process into consideration. Computational results suggest the following therapy protocol which is in accordance with experimental observations: A few high dose TILs injections are required. Then, there is a longtime drug free interval. [ABSTRACT FROM AUTHOR]