Search Results (26,590)

Trialeurodes vaporariorum Westwood poses a significant threat to vegetable and ornamental crops in temperate zones, resulting in notable reductions in yield and substantial economic burdens. In order to find compounds with high insecticidal activity against T. vaporariorum, five compounds were isolated and identified from the crude extract of Streptomyces sp. SA61. These include three new polyketides, named strekingmycins F–H (1–3); one new diterpenoid, named phenalinolactone CD8 (4); and one known compound, strekingmycin A (5). Their structures were analyzed using high-resolution electrospray ionization mass spectrometry and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy data and by comparing them with previously reported data. The insecticidal activities of compounds 1–5 against T. vaporariorum were evaluated. Among them, compound 5 exhibited the highest insecticidal activity, with an LC₅₀ of 6.949 mg/L against T. vaporariorum at 72 h using the leaf-dip method. Lower insecticidal activities were found in compounds 1–4, with LC₅₀ values of 22.817, 19.150, 16.981 and 41.501 mg/L, respectively. These data indicate that strekingmycin could be a potential candidate for a novel insecticide to control T. vaporariorum. Full article

Lead (Pb) and cadmium (Cd) are toxic pollutants that are prevalent in wastewater and pose a serious threat to the natural environment. In this study, a new immobilized bacterial microsphere (CYB-SA) was prepared from corn stalk biochar and Klebsiella grimontii by sodium alginate encapsulation and vacuum freeze-drying technology. The removal effect of CYB-SA on Pb(II) and Cd(II) in a monometallic contaminated solution was studied. The results showed that the removal of Pb(II) and Cd(II) by CYB-SA was 99.14% and 83.35% at a dosage of 2.0 g/L and pH = 7, respectively, which was 10.77% and 18.58% higher than that of biochar alone. According to the Langmuir isotherm model, the maximum adsorption capacities of Pb(II) and Cd(II) by CYB-SA at 40 °C were 278.69 mg/g and 71.75 mg/g, respectively. A combination of the kinetic model, the isothermal adsorption model, scanning electron microscopy–energy dispersive X-ray spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) analyses showed that the main adsorption mechanisms of CYB-SA encompass functional group complexation, ion exchange, electrostatic attraction and physical adsorption. The findings of this study offer practical and theoretical insights into the development of highly efficient adsorbents for heavy metals. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetrical joint inflammation, cartilage degradation, and bone erosion. This review explores the multifaceted aspects of RA pathogenesis, focusing on the dynamic interplay between innate and adaptive immune responses, genetic predisposition, and environmental triggers. The development of RA involves genetic susceptibility and trigger events such as infections, trauma, smoking, obesity, and microbiome alterations, fostering autoimmune reactions and tissue/organ destruction. The innate immune response, including toll-like receptor activation and synovial fibroblasts’ roles, contributes to the acceleration of inflammatory processes in joint tissues. Monocytes and macrophages organize and sustain chronic joint inflammation, leading to tissue damage and bone resorption, while highlighting the significance of CD14 and CD16 subsets in RA pathogenesis. In the adaptive immune response, aberrant activation and proliferation of CD4+ T cells and the role of regulatory T cells in maintaining immune tolerance are discussed. Target cytokines like TNF-α, IL-6, IL-1, IL-17, and BAFF, as well as chemokines such as CCL2, CXCL10, CCL5, and CXCL12, have emerged as critical components in managing chronic inflammation and joint damage in RA. This comprehensive overview provides insights into the pathophysiology of RA and potential therapeutic avenues, emphasizing the importance of understanding these complex immunological and genetic mechanisms for developing more effective treatment strategies. Full article

Newcastle disease virus (NDV) is an oncolytic virus whose F protein cleavage activity is associated with viral infectivity. To explore the potential of modifying F protein cleavage activity to enhance antitumor effects, we constructed a recombinant NDV LaSota strain by replacing its F protein cleavage site with that from the mesogenic Beaudette C (BC) strain using reverse genetics techniques. The resulting virus, rLaSota-BC-RFP, demonstrated significantly enhanced infectivity and tumor cell suppression on the murine melanoma B16F10 cell, characterized by higher cytotoxicity and increased apoptosis compared to its parental strain, rLaSota-RFP. In vivo, rLaSota-BC-RFP treatment of B16F10 tumors in C57BL/6 mice resulted in significant tumor growth inhibition, improved survival rate, and induction of tumor-specific apoptosis and necrosis. Additionally, the rLaSota-BC-RFP treatment enhanced immunostimulatory effects within the tumor microenvironment (TME), characterized by increased infiltration of CD4⁺ and CD8⁺ T cells and elevated levels of antitumor immune modulator cytokines, including mouse IL-12, IFN-γ, IL-15, and TNF-α, in the rLaSota-BC-RFP-treated tumor tissues. Collectively, these findings demonstrate that the mesogenic F protein cleavage site enhances the oncolytic potential of the NDV LaSota strain, suggesting that rLaSota-BC-RFP is a promising oncolytic viral vector for gene delivery in cancer immunotherapy. Full article

Immunological risk factors in recurrent pregnancy loss include autoantibodies, alterations in NK cell number and function, regulatory T cells, the human leukocyte antigen system (HLA), etc., where the treatment options aim to regulate immune dysfunction. Intralipid is a synthetic product traditionally used as a dietary supplement consisting of soybean oil combined with refined egg phospholipids. It has been shown that intralipid exerts physiologic activities, including altering immunological functions, that may benefit patients with certain types of infertility. In this review, we summarize the current state of the art of targeting NK cells and NK cell activity in women with implantation failure or/and recurrent pregnancy loss. We focus on intralipid mechanisms of action and outcomes of clinical trials regarding the efficacy and safety of intralipid infusions in women with reproductive failure. More studies are needed to reveal all the aspects of the safety and effectiveness of intralipid administration in reproductive failure treatment. Full article

L-arginine metabolism through arginases and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of Chagas disease. Infection with Trypanosoma cruzi can cause a wide spectrum of disease, ranging from acute forms contained by the host immune response to chronic ones, such as the chronic chagasic cardiomyopathy. Here, we analyzed, in an in vitro model, the ability of two T. cruzi isolates, with different degrees of virulence, to regulate the metabolism of L-arginine through arginase 1 (Arg-1) and NOS2 in macrophages and through arginase 2 (Arg-2) and NOS2 in cardiomyocytes. Stimulation of bone marrow-derived macrophages (BMMΦ), obtained from CD1 mice, with TNF-α + IFN-γ induced their polarization into classically activated macrophages (CAMΦ), which expressed functional NOS2, while stimulation with IL-4 induced their polarization into alternatively activated macrophages (AAMΦ), which expressed functional Arg-1. Interestingly, stimulation of cardiomyocytes, obtained from hearts of CD1 neonatal mice, with TNF-α + IFN-γ or IL-4 also resulted in functional NOS2 and arginase expression, as observed in CAMΦ and AAMΦ, but Arg-2 was the arginase isoform expressed instead of Arg-1. We observed that infection of BMMΦ with the more virulent T. cruzi isolate (QRO) importantly diminished NOS2 expression and nitric oxide (NO) production in CAMΦ, allowing parasite survival, while infection with the less virulent isolate (CI2) did not diminish NOS2 activity and NO production in CAMΦ to a great extent, which resulted in parasite killing. Regarding Arg-1, infection of BMMΦ with the QRO isolate significantly induced Arg-1 expression and activity in AAMΦ, which resulted in a higher parasite load than the one in the unstimulated BMMΦ. Even though infection with CI2 isolate did not increase Arg-1 expression and activity in AAMΦ, the parasite load was higher than the one in the unstimulated BMMΦ but at a lesser magnitude than that observed during infection with the QRO isolate. On the other hand, infection of cardiomyocytes with either QRO or CI2 isolates and further stimulation with TNF-α + IFN-γ inhibited NOS2 expression and NO production, leading to amelioration of infection. Surprisingly, infection of cardiomyocytes with either QRO or CI2 isolates and further stimulation with IL-4 strongly inhibited Arg-2 expression and function, which resulted in parasite loads similar to those observed in unstimulated cardiomyocytes. Our results suggest that T. cruzi isolates that exhibit variable virulence or pathogenicity degrees differentially regulate L-arginine metabolism through Arg-1/2 and NOS2 in macrophages and cardiomyocytes. Full article

Metallothioneins are multifunctional proteins implicated in various cellular processes. They have been used as biomarkers of heavy metal exposure and contamination due to their intrinsic ability to bind heavy metals and their transcriptional response to both physiological and noxious metal ions such as cadmium (Cd) and mercury (Hg). In this study, we aimed to clarify the role of iron and reactive oxygen species (ROSs) in the induction of the metallothionein system (Mtt) in the ciliate protozoan Tetrahymena thermophila. We investigated the relative mRNA abundances of the metallothionein genes Mtt1, Mtt2/4, and Mtt5, revealing for the first time their responsiveness to iron exposure. Furthermore, by using inhibitors of superoxide dismutase (SOD) and catalase (CAT), alone or in combination with iron, we highlighted the roles of superoxide ion and endogenous hydrogen peroxide, as well as the complex interplay between the metal and ROSs. These results enhance our understanding of the metallothionein system in ciliates and suggest that ROSs may be a primary evolutionary driver for the selection of these proteins in nature. Full article

As an important member of innate immunity, macrophages show remarkable plasticity and heterogeneity, and play an important role in immune regulation, tissue development, homeostasis of the internal environment and injury repair. However, the excessive activation of macrophages is closely related to the occurrence and development of many diseases. The prenylated flavonoid structure is one of the characteristic structures isolated from Sophora flavescens, with anti-inflammatory, anti-tumor, anti-allergy and other effects. In this study, the effects of (2R)-3β,7,4′-trihydroxy-5-methoxy-8-prenylflavanone (TMP), a prenylated dihydroflavonol, on the polarization and phagocytosis of macrophages were systematically studied. In LPS-induced M1-type macrophages, TMP dose-dependently inhibited the expression of COX-2, iNOS and the secretion of NO, IL-1β, IL-6 and IL-18, showing an inhibitory effect on M1 polarization. Further experiments revealed that it was related to the inhibition of TLR4-related AKT/mTOR, MAPK and NF-κB signaling pathways; in IL-4-induced M2-type macrophages, TMP down-regulated the expression of M2-related Arg1, IL-10, TGF-β, CD206 and CD163, as well as the phosphorylation levels of AKT1 and STAT6. For macrophages in a physiological state, it was very important for cells to return from a stress state to a phenotypic stability in the M0 state. These results indicated that TMP negatively regulated the M1/M2 polarization of macrophages, and made them tend to M0 homeostasis, which might provide new theoretical and data support for explaining the anti-inflammatory immunoregulatory activity of Sophora flavescens. Full article

Conserved influenza virus proteins, such as the hemagglutinin stem domain (HA2), nucleoprotein (NP), and matrix protein (M), are the main targets in the development of universal influenza vaccines. Previously, we constructed a recombinant vaccine protein Flg-HA2-2-4M2ehs containing the extracellular domain of the M2 protein (M2e) and the aa76–130 sequence of the second HA subunit as target antigens. It demonstrated immunogenicity and broad protection against influenza A viruses after intranasal and parenteral administration. This study shows that CD8+ epitopes of NP, inserted into a flagellin-fused protein carrying M2e and HA2, affect the post-vaccination immune humoral response to virus antigens without reducing protection. No differences were found between the two proteins in their ability to stimulate the formation of follicular Th in the spleen, which may contribute to a long-lasting antigen-specific humoral response. The data obtained on Balb/c mice suggest that the insertion of CTL NP epitopes into the flagellin-fused protein carrying M2e and HA2 reduces the antibody response to M2e and A/H3N2. In C57Bl6 mice, this stimulates the formation of NP-specific CD8+ Tem and virus-specific mono- and multifunctional CD4+ and CD8+ Tem in the spleen and completely protects mice from influenza virus subtypes A/H1N1pdm09 and A/H3N2. Full article

Introduction: End-stage renal disease (ESRD) results in immune dysfunction that is characterized by both systemic inflammation and immune incompetence, leading to impaired responses to vaccination. Methods: To unravel the complex regulatory immune interplay in ESRD, we performed the network-based transcriptomic profiling of ESRD patients on maintenance hemodialysis (HD) and matched healthy controls (HCs) who received the two-dose regimen of the COVID-19 mRNA vaccine BNT162b2. Results: Co-expression networks based on blood transcription modules (BTMs) of genes differentially expressed between the HD and HC groups revealed co-expression patterns that were highly similar between the two groups but weaker in magnitude in the HD compared to HC subjects. These networks also showed weakened coregulation between BTMs within the dendritic cell (DC) family as well as with other BTM families involved with innate immunity. The gene regulatory networks of the most enriched BTMs, likewise, highlighted weakened targeting by transcription factors of key genes implicated in DC, natural killer (NK) cell, and T cell activation and function. The computational deconvolution of immune cell populations further bolstered these findings with discrepant proportions of conventional DC subtypes, NK T cells, and CD8+ T cells in HD subjects relative to HCs. Conclusion: Altogether, our results indicate that constitutive inflammation in ESRD compromises the activation of DCs and NK cells, and, ultimately, their mediation of downstream lymphocytes, leading to a delayed but intact immune response to mRNA vaccination. Full article

This study investigates the presence of potentially toxic elements (PTEs) in lettuce (Lactuca sativa L.) grown in urban gardens in a highly industrialized city in Brazil and evaluates the effectiveness of different washing methods in reducing contamination. Ten elements (arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), vanadium (V), and zinc (Zn)) were analyzed for their concentration, and a health risk assessment was performed. The results showed that Pb concentrations in lettuce from gardens near the Capuava Petrochemical Complex reached 0.77 mg kg⁻¹, exceeding both national and international safety limits. The most effective washing procedure involved the use of sodium hypochlorite, which reduced As by 46%, Pb by 48%, and V by 52%. However, elements such as Ba, Cd, Cr, and Ni showed limited reductions of less than 10% across all washing methods. Health risk assessments revealed a particular concern for children, with the total cancer risk (TCR) exceeding acceptable limits in some gardens. Isotopic analysis of Pb revealed that atmospheric pollution from gasoline emissions and industrial activities were the primary sources of contamination. The elevated levels of Pb, Cr, and As highlight the need for targeted health education in local communities, especially regarding the importance of proper washing techniques. Risk management strategies, including improved contamination control and public awareness, are crucial to minimize exposure to these harmful elements, particularly in vulnerable populations like children. Full article

Melanoma is one of the most common tumors worldwide, and new approaches and antitumor drugs for therapy are being investigated. Among the promising biomolecules of natural origin for antitumor research are gastropodan hemocyanins—highly immunogenic multimeric glycoproteins used as antitumor agents and components of therapeutic vaccines in human and mouse cancer models. A murine melanoma model established in C57BL/6 mice of the B16F10 cell line was used to study anticancer modified oxidized hemocyanins (Ox-Hcs) that were administered to experimental animals (100 μg/mouse) under different regimens: mild, intensive, and with sensitization. The solid tumor growth, antitumor response, cell infiltration in tumors, and survival were assessed using flow cytometry, ELISA, and cytotoxicity assays. Therapy with Ox-RtH or Ox-HaH resulted in the generation of enhanced specific immune response (increased levels of tumor-infiltrated mature NK cells (CD27+CD11b+) in sensitized groups and of macrophages in the intensively immunized animals) and tumor suppression. Beneficial effects such as delayed tumor incidence and growth as well as prolonged survival of tumor-bearing animals have been observed. High levels of melanoma-specific CTLs that mediate cytotoxic effects on tumor cells; tumor-infiltrating IgM antibodies expected to enhance antibody-dependent cellular cytotoxicity; type M1 macrophages, which stimulate the Th1 response and cytotoxic cells; and proinflammatory cytokines, were also observed after Ox-Hcs administration. The modified Hcs showed strong antitumor properties in different administration regimens in a murine model of melanoma with potential for future application in humans. Full article

Lupus nephritis (LN) is a common clinical manifestation of systemic lupus erythematosus (SLE). Our study aims to quantitatively analyze CD4+ and CD8+ lymphocytes in different areas and LN classes and describe a specific distribution pattern that is correlated with the severity of LN-specific lesions. In total, 53 LN renal biopsies were immunohistochemically investigated using anti-CD4 and anti-CD8 antibodies. T lymphocytes were counted in 3 areas, including intraglomerular, periglomerular, and interstitial regions. The severity of glomerular and tubulo-interstitial lesions was assessed using an original semi-quantitative algorithm based on the renal corpuscle score (RC_S) and the tubulo-interstitial score (TI_S). The number of CD8+ T lymphocytes was higher than that of CD4+ T lymphocytes in each of the three areas and in each LN class, showing statistically significant differences. ANOVA analysis of all LN classes showed significant differences between periglomerular and interstitial CD4+ and CD8+ T lymphocytes, respectively. Irrespective of location, the number of CD8+ T lymphocytes statistically correlates with the RC_S and the TI_S; no significant correlations were found between the number of CD4+ T lymphocytes and the RC_S and the TI_S for all three considered areas. Our data provide strong evidence supporting the major role of CD8+ lymphocytes in LN lesion progression, with CD4+ lymphocytes playing a limited role. Full article

Post-operative fibrosis of the filtering bleb limits the success of glaucoma filtration surgery (GFS). To minimise subconjunctival scarring following GFS, treatment with antimetabolites such as Mitomycin C (MMC) has become standard practice; however, their use is associated with considerable side effects. This study aimed to investigate the anti-scarring properties of 3′,4′-dihydroxyflavonol (DiOHF). GFS was performed in New Zealand white rabbits who received eye drops of DiOHF three times daily and vehicle eye drops after surgery (n = 5) or a single intraoperative treatment of MMC (n = 5). Blebs were imaged immediately following surgery and on days 7, 15, 21, and 28 for clinical examination. On day 28, eyes were harvested to assess collagen deposition, expression of α-SMA, oxidative stress, angiogenesis, fibroblast activity, and inflammation in the conjunctiva/Tenon’s layer. At 7 and 28 days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or vehicle-treated blebs. On day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31 expression, Vimentin expression, and CD45 expression compared to the vehicle control. No difference was observed in 3-Nitrotyrosine or αSMA expression between treatment groups. Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS, which was comparable to MMC. DiOHF may be a safer and more effective wound-modulating agent than conventional antifibrotic therapy in GFS. Full article

Cadmium (Cd) pollution in soil has become a huge problem for agricultural production in China and even the world. Passivation and phytoremediation are two important remediation technologies for Cd pollution. In this study, the cadmium-contaminated and phosphorus-poor farmland soil around a mining area in Huainan was taken as the research object, and the remediation effect of biochar and phosphorus-containing materials on soil cadmium pollution was discussed. The results showed that the combined application of biochar and phosphorus-containing materials significantly reduced the pH of non-rhizosphere soil and rhizosphere soil, and increased the content of soil dissolved organic carbon (DOC). The combined application of biochar and phosphorus-containing materials significantly reduced soil pore water Cd and soil available Cd. In addition, both a single application of biochar and synergistic application of biochar and phosphorus-containing materials significantly increased the biomass of aboveground and underground parts of amaranth and soil urease and catalase activities. Phosphorus application reduced the bioavailability of Cd in soil. With the increase in phosphorus application, the content of available Cd in soil decreased significantly, and there was a certain negative correlation between Cd content and phosphorus content in plants. The abundance of beneficial microorganisms such as Ochrobactrum, Anaerolinea, Achromobacter, and Cellvibrio in soil was significantly increased after the synergistic application of biochar and phosphorus-containing materials. Full article