Antimicrobial peptides (AMPs) or host defense peptides protect the host against various pathogens such as yeast, fungi, viruses and bacteria. AMPs also display immunomodulatory properties ranging ...from the modulation of inflammatory responses to the promotion of wound healing. More interestingly, AMPs cause cell disruption through non-specific interactions with the membrane surface of pathogens. This is most likely responsible for the low or limited emergence of bacterial resistance against many AMPs. Despite the increasing number of antibiotic-resistant bacteria and the potency of novel AMPs to combat such pathogens, only a few AMPs are in clinical use. Therefore, the current review describes (i) the potential of AMPs as alternatives to antibiotics, (ii) the challenges toward clinical implementation of AMPs and (iii) strategies to improve the success rate of AMPs in clinical trials, emphasizing the lessons we could learn from these trials.
The chemical composition of PM2.5 and cellular effects from exposure to fine aerosol extracts were studied for samples collected in Beijing, Tianjin, Shijiazhuang, and Hengshui, China in winter 2015. ...Effects of priority polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivatives (OPAHs) in PM2.5 on cell cultures were a major focus of the study. Total quantified PAHs and OPAHs at Shijiazhuang and Hengshui were higher than at Beijing and Tianjin, and benz(a)anthracene, chrysene and 1,8-naphthalic anhydride were the most abundant species. Exposure to PM2.5 extracts caused a concentration-dependent decline in cell viability and a dose-dependent increase in nitric oxide production. Two cytokines, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), also increased when A549 test cells were exposed to PM2.5 extracts. PAHs and OPAHs in PM2.5 can potentially cause cell damage and induce cytotoxicity and pro-inflammatory responses: benzo(a)anthracene-7,12-dione was highly correlated with NO production, dibenz(a,h)anthracene and 1,4-chrysenequinone were correlated with TNF-α production, and 1-naphthaldehyde was significantly correlated with IL-6 production. The study provides a new approach for evaluating relationships between air-quality and cell toxicity with respect to specific chemicals.
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•PAHs and OPAHs were qualified in Beijing-Tianjin-Hebei region.•Cell viability of A549 exposed to PM2.5 showed a concentration-dependent decline.•PM2.5 exhibited dose-dependent increases in NO, TNF-α and IL-6 productions.•DBA and 1,4-CRQ were well correlated with TNF-α, and 1-NAD was correlated with IL-6.
Exposure to PAHs and OPAHs associated with fine aerosol particles may induce cytotoxic and pro-inflammatory responses in vitro.
Effector CD8+ T cells are typically thought to be a homogenous group of cytotoxic cells that produce interferon-(IFN) γ. However, recent findings have challenged this notion because multiple subsets ...of CD8+ T cells have been described, each with distinct effector functions and cytotoxic potential. These subsets, referred to as the Tc subsets, have also been detected in tumor microenvironments (TMEs), where they potentially influence the antitumor response and patient outcomes. In this review, we highlight the prevalence and roles of Tc subsets in the TME. We also discuss their therapeutic applications in the context of adoptive immunotherapy to treat cancer.
There are multiple subsets of CD8+ T cells, not all of which have cytotoxic function and produce IFN-γ.A variety of Tc subsets have been detected within the TME and, depending on the subset, can be either positively or negatively correlated with prognosis.In the context of adoptive immunotherapy to treat cancer, the degree of tumor control is greatly influenced by the subset of T cells transferred.
Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 ...antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity. As such, various strategies have focused on producing afucosylated antibodies to improve therapeutic efficacy. This review discusses the relevance of antibody core fucosylation to ADCC, different strategies to produce afucosylated antibodies, and an update of afucosylated antibody drugs currently undergoing clinical trials as well as those that have been approved.
Magnetic nanocomposites containing iron oxide and gold components take great attention last years because of their relative biocompatibility and the ability to combine the magnetic properties of iron ...and the chemical bonding properties of gold for the possible drug delivery or diagnostics for various diseases. However, such particles have some toxicity to living cells, and the effect depends on many factors, including size, shape, the ratio of components in the composites, and the type of cells affected. And thus, the search for compositions and technologies for producing iron-gold particles with improved properties and reduced cytotoxicity remains relevant. The aim of the study was to synthesize and characterize Fe3O4/Au nanocomposites and evaluate their influence on living cells using the example of cell line HEK293.
Fe3O4 nanoparticles (NPs) were synthesized by co-precipitation of Fe2+/Fe3+ water solution in alkaline conditions and then boiled with HAuCl4 in 0.1 M sodium citrate. The NPs properties were estimated by transmission electron microscopy (TEM), vibration magnetometry and ferromagnetic resonance (FMR).
According to magnetometric measurements, nanoparticles are mainly in a superparamagnetic state. By fitting magnetization curves, the magnetic characteristics of nanoparticles were determined: saturation magnetization (59.3 emu/g) and magnetic anisotropy constant (K = 0.86·105 erg/cm3). The average particle size estimated from magnetic measurements was 8.7 nm. Considering the presence of a magnetically dead layer, this is in good agreement with the TEM results. The temperature dependence of the FMR linewidth was analyzed using two models. As a result, the parameters MSV and K/MS were determined. The models used showed good agreement. The values of the anisotropy constant (K = 1.06·105 erg/cm3) and the average particle size (6.8 nm) are estimated.
The effect of the NPs on the HEK293 cells was studied by MTT-assay, flow cytometry and RT-PCR. The exposure with the NPs lead to a significant decrease of cell metabolic activity in HEK293 cell culture, but this effect was not accompanied by cell death. It was shown that the expression of antioxidant enzymes SOD1 and GPX1 was reduced at the mRNA stage. So the NPs synthesized may affect gene expression and metabolism of HEK293 cells, but this does not have fatal consequences for cell viability.
•Magnetic nanocomposites of Fe3O4/Au were synthesized.•Magnetic properties of nanoparticles were studied using magnetometry and FMR.•Magnetic Fe3O4/Au particles can reduce metabolic activity of living cells.•Fe3O4/Au nanocomposites affect the mRNA level of SOD1 and GPX1 genes.
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in ...acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.
Trastuzumab, a targeted anti-human epidermal-growth-factor receptor-2 (HER2) monoclonal antibody, represents a mainstay in the treatment of HER2-positive (HER2
) breast cancer. Although trastuzumab ...treatment is highly efficacious for early-stage HER2
breast cancer, the majority of advanced-stage HER2
breast cancer patients who initially respond to trastuzumab acquire resistance to treatment and relapse, despite persistence of HER2 gene amplification/overexpression. Here, we sought to leverage HER2 overexpression to engage antibody-dependent cellular phagocytosis (ADCP) through a combination of trastuzumab and anti-CD47 macrophage checkpoint immunotherapy. We have previously shown that blockade of CD47, a surface protein expressed by many malignancies (including HER2
breast cancer), is an effective anticancer therapy. CD47 functions as a "don't eat me" signal through its interaction with signal regulatory protein-α (SIRPα) on macrophages to inhibit phagocytosis. Hu5F9-G4 (magrolimab), a humanized monoclonal antibody against CD47, blocks CD47's "don't eat me" signal, thereby facilitating macrophage-mediated phagocytosis. Preclinical studies have shown that combining Hu5F9-G4 with tumor-targeting antibodies, such as rituximab, further enhances Hu5F9-G4's anticancer effects via ADCP. Clinical trials have additionally demonstrated that Hu5F9-G4, in combination with rituximab, produced objective responses in patients whose diffuse large B cell lymphomas had developed resistance to rituximab and chemotherapy. These studies led us to hypothesize that combining Hu5F9-G4 with trastuzumab would produce an anticancer effect in antibody-dependent cellular cytotoxicity (ADCC)-tolerant HER2
breast cancer. This combination significantly suppressed the growth of ADCC-tolerant HER2
breast cancers via Fc-dependent ADCP. Our study demonstrates that combining trastuzumab and Hu5F9-G4 represents a potential new treatment option for HER2
breast cancer patients, even for patients whose tumors have progressed after trastuzumab.
Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage ...hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.
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•trans-Differentiation of cytotoxic Th17 to Th1 cells promotes liver pathology•CX3CR1+CD8Teff cells inhibit fibrosis by granzyme-mediated killing of fibroblasts•Defective induction of hepatic B cell tolerance promotes autoimmunity in infants•B-cell-modifying therapies promote immune recovery in infants with biliary atresia
Liver immune profiling in infants with biliary atresia suggests B-cell-modifying therapies may alleviate liver pathology
Zinc oxide (ZnO) is the most commonly used nanoparticles among different nanoparticles. Its applications ranged from personal care products, sensors, antibacterial creams, and biomedical ...applications. The broad range of applications raises concern in regards to their potential toxicity. Therefore, it is required to understand their toxicity mechanism and pattern on various levels. The primary aim of this review is to summarize the cytotoxicity, genotoxicity, neurotoxicity, and developmental toxicity of ZnO nanoparticles in various kinds of cells in vitro and in vivo. Literatures available on ZnO nanoparticles toxicity suggest that dissolution, organism dependent cellular uptake, generation of reactive oxygen species (ROS), and induced inflammatory responses seem to be common factors which govern the toxicity of ZnO nanoparticles.
The aim of this study was to determine the nutritive value of edible insects and their in vitro cytotoxicity assays. The content of protein, fat, carbohydrates, ash, fiber, minerals, amino acids, and ...fatty acids in adult cricket (Gryllodes sigillatus), larvae of mealworm (Tenebrio molitor), and adult locust (Schistocerca gregaria) were analyzed. The protein content ranged from 52.35 to 76%. The fat percentage was in the range of 12.97–24.7%. Energy contribution varied from 1821 to 1896kJ/100g. Their amino acid profile was compared with the WHO/FAO/UNU Pattern (WHO, 2007). The highest degree of hydrolysis (DH) was noted in baked Gryllodes sigillatus (37.76%). All species were very rich in magnesium, copper, iron, and zinc and the mineral content was compared to recommended daily intakes (mg/day). The hydrolysates from raw, cooked, and baked insects were significantly stimulated or inhibited proliferation of human skin fibroblasts CRL-2522.
•Edible insects are a good source of the valuable nutritional compounds.•Edible insects' protein is a rich source of the essential amino acids.•The heat treatment process affects the degree of hydrolysis.•Some edible insects have the ability for stimulation of human skin fibroblast.
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