Extracellular vesicles derived from plasmodium-infected red blood cells alleviate cerebral malaria in plasmodium berghei ANKA-infected C57BL/6J mice.

RTS,S is the first malaria vaccine recommended for implementation among young children at risk. However, vaccine efficacy is modest and short-lived. To mitigate the risk of cerebral malaria (CM) among children under the age of 5, it is imperative to develop new vaccines. EVs are potential vaccine candidates as they obtain the ability of brain-targeted delivery and transfer plasmodium antigens and immunomodulators during infections. This study extracted EVs from BALB/c mice infected with Plasmodium yoelii 17XNL (P.y17XNL). C57BL/6J mice were intravenously immunized with EVs (EV-I.V. + CM group) or subcutaneously vaccinated with the combination of EVs and CpG ODN-1826 (EV + CPG ODN-S.C. + CM group) on days 0 and 20, followed by infection with Plasmodium berghei ANKA (P.bANKA) on day 20 post-second immunization. We monitored Parasitemia and survival rate. The integrity of the Blood-brain barrier (BBB) was examined using Evans blue staining.The levels of cytokines and adhesion molecules were evaluated using Luminex, RT-qPCR, and WB. Brain pathology was evaluated by hematoxylin and eosin and immunohistochemical staining. The serum levels of IgG, IgG1, and IgG2a were analyzed by enzyme-linked immunosorbent assay. Compared with those in the P.bANKA-infected group, parasitemia increased slowly, death was delayed (day 10 post-infection), and the survival rate reached 75 %-83.3 % in the EV-I.V. + ECM and EV + CPG ODN-S.C. + ECM groups. Meanwhile, compared with the EV + CPG ODN-S.C. + ECM group, although parasitemia was almost the same, the survival rate increased in the EV-I.V. + ECM group.Additionally, EVs immunization markedly downregulated inflammatory responses in the spleen and brain and ameliorated brain pathological changes, including BBB disruption and infected red blood cell (iRBC) sequestration. Furthermore, the EVs immunization group exhibited enhanced antibody responses (upregulation of IgG1 and IgG2a production) compared to the normal control group. EV immunization exerted protective effects, improving the integrity of the BBB, downregulating inflammation response of brain tissue, result in reduces the incidence of CM. The protective effects were determined by immunological pathways and brain targets elicited by EVs. Intravenous immunization exhibited better performance than subcutaneous immunization, which perhaps correlated with EVs, which can naturally cross BBB to play a better role in brain protection.

Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Essential Oil of Matricaria chamomilla Alleviate Psoriatic-Like Skin Inflammation by Inhibiting PI3K/Akt/mTOR and p38MAPK Signaling Pathway.

Background: The traditional Matricaria chamomilla L. has been used to treat dermatitis for thousands of years. Due to emerging trends in alternative medicine, patients prefer natural remedies to relieve their symptoms. Therefore, finding safe and effective plant medicines for topical applications on the skin is an important treatment strategy for dermatologists. German chamomile (Matricaria chamomilla L.) from the Compositae family is a famous medicinal plant, often known as the "star of medicinal species."However, the function of Matricaria chamomilla essential oil on skin inflammation has not been thoroughly examined in earlier research. Methods: GC-MS analyzed the components of MCEO, and this study explored the anti-inflammation effects of MCEO on psoriasis with network pharmacological pathway prediction. Following this, we used clinical samples of psoriasis patients to confirm the secretory characteristic of relative inflammatory markers. The therapeutic effect of MCEO on skin inflammation was detected by examination of human keratinocytes HaCaT. At the same time, we prepared imiquimod-induced psoriatic-like skin inflammation in mice to investigate thoroughly the potential inhibition functions of MCEO on psoriatic skin injury and inflammation. Results: MCEO significantly reduced interleukin-22/tumor necrosis factor α/lipopolysaccharide-stimulated elevation of HaCaT cell inflammation, which was correlated with downregulating PI3K/Akt/mTOR and p38MAPK pathways activation mediated by MCEO in HaCaT cells treated with IL-22/TNF-α/LPS. Skin inflammation was evaluated based on the PASI score, HE staining, and relative inflammatory cytokine levels. The results showed that MCEO could significantly contribute to inflammatory skin disease treatment. Conclusion: MCEO inhibited inflammation in HaCaT keratinocytes induced by IL-22/TNF-α/LPS, the potential mechanisms associated with inhibiting excessive activation and crosstalk between PI3K/Akt/mTOR and p38MAPK pathways. MCEO ameliorated skin injury in IMQ-induced psoriatic-like skin inflammation of mice by downregulating the levels of inflammatory cytokines but not IL-17A. Thus, anti-inflammatory plant drugs with different targets with combined applications were a potential therapeutic strategy in psoriasis.

Quantitative characterization of resident' exposure to typical semi-volatile organic compounds (SVOCs) around a non-ferrous metal smelting plant.

To comprehensively characterize residents' exposure to major semi-volatile organic compounds (SVOCs), samples of indoor floor wipes, size-segregated airborne particles, gaseous air, food, and paired skin wipes were simultaneously collected from residential areas around a large non-ferrous metal smelting plant as compared with the control areas, and three typical SVOCs (including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and halogenated PAHs (HPAHs)) were determined. Comparison and correlation analysis among matrices indicated PAHs were the major contaminants emitted from metal smelting activities compared to HPAHs and PCBs, with naphthalene verified as the most important characteristic compound, and their accumulation on skin may be a comprehensive consequence of contact with floor dust and air. While patterns of human exposure pathways for the SVOCs were found to be clearly correlated to their vapor pressure, dermal absorption was the major contributor (51.1-76.3%) to total carcinogenic risk (TCR) of PAHs and HPAHs for surrounding residents, especially for low molecular weight PAHs, but dietary ingestion (98.6%) was the dominant exposure pathway to PCBs. The TCR of PAHs exceeded the acceptable level (1 × 10-4), implying smelting activities obviously elevated the health risk. This study will serve developing pertinent exposure and health risk prevention measures.

Exosome-derived long noncoding RNAs: Mediators of host-Plasmodium parasite communication.

Overcoming challenges associated with malaria eradication proves to be a formidable task due to the complicated life cycle exhibited by the malaria parasite and the lack of safe and enduring vaccines against malaria. Investigating the interplay between Plasmodium parasites and their mammalian hosts is crucial for the development of novel vaccines. Long noncoding RNAs (lncRNAs) derived from Plasmodium parasites or host cells have emerged as potential signaling molecules involved in the trafficking of proteins, RNA (mRNAs, miRNAs, and ncRNAs), and DNA. These lncRNAs facilitate the interaction between hosts and parasites, impacting normal physiology or pathology in malaria-infected individuals. Moreover, they possess the capacity to regulate immune responses and associated signaling pathways, thus potentially influencing chromatin organization, epigenetic modifications, mRNA processing, splicing, and translation. However, the functional role of exosomal lncRNAs in malaria remains poorly understood. This review offers a comprehensive analysis of lncRNA and exosomal lncRNA profiles during malaria infection. It presents an overview of recent progress in elucidating the involvement of exosomal lncRNAs in host-parasite interactions. Additionally, potential exosomal lncRNAs linked to the domains of innate and adaptive immunity in the context of malaria are proposed. These findings may contribute to the discovery of new diagnostic and therapeutic strategies for malaria. Furthermore, the need for additional research was highlighted that aimed to elucidate the mechanisms underlying lncRNA transportation into host cells and their targeting of specific genes to regulate the host's immune response. This knowledge gap presents an opportunity for future investigations, offering innovative approaches to enhance malarial control. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease.

THE ALARMIN EFFECT OF HMGB1/RIP3 ON TRANSFUSION-RELATED ACUTE LUNG INJURY VIA TLR4/NF-ΚB OR MAPK PATHWAY.

ABSTRACT: Nonantibody-mediated transfusion-related acute lung injury (TRALI) may account for up to 25% of TRALI cases. This indicates the need for further research to understand the pathophysiological mechanisms involved beyond antibody mediation fully. During this research, a TRALI rat model was developed using the trauma-blood loss-massive transfusion method. The severity of pulmonary edema was checked via measurement of lung histopathological changes and the amount of Evans blue dye fluid and bronchoalveolar lavage fluid protein leakage. In addition, potential mechanisms of pathophysiological pathways and inflammation cascades were investigated in TRALI rats in vivo . The findings indicated that TRALI increased inflammatory cytokines and triggered elevated levels of high-mobility group box 1 (HMGB1)/receptor-interacting protein kinase 3 (RIP3), apoptosis protein, and mRNAs in the TM (TRALI model) group as opposed to the normal control. Furthermore, TRALI activated the toll-like receptor 4/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways, which partially regulated the inflammatory response in the TRALI rats. A significant increase was observed in the inflammatory mediators HMGB1 and RIP3 during the early stages of TRALI, suggesting that these mediators could be used as diagnostic markers for TRALI. In addition, HMGB1 and RIP3 promoted the inflammatory response by stimulating the toll-like receptor 44/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways in the lung tissue of rats. Identifying efficient agents from inflammatory mediators such as alarmin can be an innovative scheme for diagnosing and preventing TRALI. These findings give HMGB1 and RIP3 a strong theoretical and experimental foundation for clinical use.

The immunity modulation of transforming growth factor-ß in malaria and other pathological process.

The main causative agent of malaria in humans is Plasmodium falciparum, which is spread through biting Anopheles mosquitoes. Immunoregulation in the host involving the pleiotropic cytokine transforming growth factor-ß (TGF-ß) has a vital role in controlling the immune response to P. falciparum infection. Based on a search of the published literature, this study investigated the correlation between malaria and immune cells, specifically the role of TGF-ß in the immune response. The studies analyzed showed that, when present in low amounts, TGF-ß promotes inflammation, but inhibits inflammation when present in high concentrations; thus, it is an essential regulator of inflammation. It has also been shown that the quantity of TGF-ß produced by the host can influence how badly the parasite affects the host. Low levels of TGF-ß in the host prevent the host from being able to manage the inflammation that Plasmodium causes, which results in a pathological situation that leaves the host vulnerable to fatal infection. Additionally, the amount of TGF-ß fluctuates throughout the host's Plasmodium infection. At the beginning of a Plasmodium infection, TGF-ß levels are noticeably increased, and as Plasmodium multiplies quickly, they start to decline, hindering further growth. In addition, it is also involved in the growth, proliferation, and operation of various types of immune cell and correlated with levels of cytokines associated with the immune response to malaria. TGF-ß levels were positively connected with the anti-inflammatory cytokine interleukin-10 (IL-10), but negatively correlated with the proinflammatory cytokines interferon-γ (IFN-γ) and IL-6 in individuals with severe malaria. Thus, TGF-ß might balance immune-mediated pathological damage and the regulation and clearance of infectious pathogens. Numerous domestic and international studies have demonstrated that TGF-ß maintains a dynamic balance between anti-inflammation and pro-inflammation in malaria immunity by acting as an anti-inflammatory factor when inflammation levels are too high and as a pro-inflammatory factor when inflammation levels are deficient. Such information could be of relevance to the design of urgently needed vaccines and medications to meet the emerging risks associated with the increasing spread of malaria and the development of drug resistance.

Distribution, sources and health risks of heavy metals in indoor dust across China.

The potential effects of heavy metals on human health have attracted increasing attention as most people spend up to 90% of their time indoors. Human exposure to heavy metals in indoor dust have only been characterised for limited regions in China, and full-scale data for different functional areas are not available. Therefore, this review analysed the concentrations, contamination characteristics, and potential health risks of seven heavy metals (including zinc (Zn), lead (Pb), copper (Cu), chromium (Cr), nickel (Ni), arsenic (As), and cadmium (Cd)) in indoor dust at 3392 sampling sites in 55 cities across 27 provincial regions of China based on literature data. Results revealed that the median heavy metal concentrations in indoor dust throughout China decreased in the following order: Zn > Pb > Cu > Cr > Ni > As > Cd. Traffic emissions and decorative materials are the primary sources of heavy metal pollution in indoor dust. No considerable non-carcinogenic risk was found for Zn, Cu, Cr, Ni, and Cd in indoor dust, while Pb and As exhibited potential non-carcinogenic risks to children, primarily distributed in cities across Southern China. Meanwhile, the carcinogenic risks posed by Cr and Ni were higher than those posed by As and Cd, especially in Southern China. Therefore, effective measures in Southern China should prioritised for controlling Pb, Cr, Ni and As pollution in indoor dust to reduce human health risk. This review is useful for policy decision-making and protecting human from exposure to heavy metals in indoor dust across China.