Manganese accumulation in red blood cells as a biomarker of manganese exposure and neurotoxicity.

Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.

Expression levels of key immune indicators and immune checkpoints in manganese-exposed rats.

Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.

Changes in serum TIM-3 and complement C3 expression in workers due to Mn exposure.

Mn (Manganese, Mn) is an essential trace element involved in various biological processes such as the regulation of immune, nervous and digestive system functions. However, excessive Mn exposure can lead to immune damage. Occupational workers in cement and ferroalloy manufacturing and other related industries are exposed to low levels of Mn for a long time. Mn exposure is one of the important occupational hazards, but the research on the effect of Mn on the immune system of the occupational population is not complete, and there is no reliable biomarker. Therefore, this study aimed to evaluate the immunotoxicity of Mn from the soluble immune checkpoint TIM-3 (T-cell immunoglobulin and mucin containing protein 3, TIM-3) and complement C3. A total of 144 Mn-exposed workers were recruited from a bus manufacturing company and a railroad company in Henan Province. An inductively coupled plasma mass spectrometer was used to detect the concentration of RBC Mn (Red blood cell Mn, RBC Mn), and ELISA kits were used to detect serum complement C3 and TIM-3. Finally, the subjects were statistically analyzed by dividing them into low and high Mn groups based on the median RBC Mn concentration. We found that Mn exposure resulted in elevated serum TIM-3 expression and decreased complement C3 expression in workers; that serum TIM-3 and complement C3 expression showed a dose-response relationship with RBC Mn; and that the mediating effect of complement C3 between RBC Mn and TIM-3 was found to be significant. The above findings indicate that this study has a preliminary understanding of the effect of Mn exposure on the immune system of the occupational population exposed to Mn, and complement C3 and TIM-3 may be biomarkers of Mn exposure, which may provide clues for the prevention and control of Mn occupational hazards.

Benchmark dose estimation based on oxidative damage in Chinese workers exposed to benzene series compounds.

This study evaluated the effects of BTEX exposure on oxidative stress; it analyzed the correlation between oxidative stress and peripheral blood counts and estimated the benchmark dose (BMD) of BTEX compounds. This study recruited 247 exposed workers and 256 controls; physical examination data were collected and serum oxidative stress levels were measured. Relationships between BTEX exposure and biomarkers were analyzed using Mann-Whitney U, generalized linear model, and chi-square trend tests. Environmental Protection Agency Benchmark Dose Software was used to calculate the BMD and lower confidence limit of the BMD (BMDL) for BTEX exposure. The total antioxidant capacity (T-AOC) correlated positively with peripheral blood counts, and negatively with the cumulative exposure dose. On using T-AOC as the outcome variable, the estimated BMD and BMDL for BTEX exposure were 3.57 mg/m3 and 2.20 mg/m3, respectively. Based on T-AOC, the calculated occupational exposure limit of BTEX was 0.055 mg/m3.

EFFECT OF EXOSOMES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS ON PROGRAMMED CELL DEATH IN BLAST-INDUCED LUNG INJURY IN RATS.

ABSTRACT: Blast lung injuries (BLIs) are frequent because of industrial accidents and terrorist groups. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs (BMSCs-Exo) have become a hot topic in modern biology because of their significance in damage healing, immune regulation, and gene therapy. The aim of this study is to investigate the effect of BMSCs and BMSCs-Exo on BLI in rats caused by gas explosion. Here, BMSCs and BMSCs-Exo were transplanted into BLI rats via tail vein and then evaluated pathological alterations, oxidative stress, apoptosis, autophagy, and pyroptosis in the lung tissue. Through histopathology and changes in malondialdehyde (MDA) and superoxide dismutase (SOD) contents, we discovered that oxidative stress and inflammatory infiltration in the lungs were significantly reduced by BMSCs and BMSCs-Exo. After treatment with BMSCs and BMSCs-Exo, apoptosis-related proteins, such as cleaved caspase-3 and Bax, were significantly decreased, and the ratio of Bcl-2/Bax was significantly increased; the level of pyroptosis-associated proteins, including NLRP3, GSDMD-N, cleaved caspase-1, IL-1ß, and IL-18, were decreased; autophagy-related proteins, beclin-1 and LC3, were downregulated while P62 was upregulated; the number of autophagosomes was decreased. In summary, BMSCs and BMSCs-Exo attenuate BLI caused by gas explosion, which may be associated with apoptosis, aberrant autophagy, and pyroptosis.

Lysophosphatidylcholine acyltransferase 1 alleviates silica-induced pulmonary fibrosis by modulating lipid metabolism.

Silicosis is an incurable lung disease that can progress even when exposure to silica dust has ended. Lipid metabolism plays an important role in the occurrence and development of silicosis. However, the mechanistic details have not been fully elucidated. This was investigated in the current study by high-performance liquid chromatography-mass spectrometry-based lipidomic analysis of lung tissue in a mouse model of silicosis. Lipid profiles and key metabolic enzymes were compared between silica and control groups. The lipidomic analysis revealed differentially-expressed lipids in the lungs of silicosis mice compared with controls. Among the identified lipid metabolism-related enzymes, the expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) was significantly down-regulated at the transcript and protein levels. LPCAT1 overexpression in vivo using adeno-associated virus altered the balance between phosphatidylcholine and lysophosphatidylcholine and inhibited the development of silicosis in mice. These results indicate that LPCAT1 dysregulation leads to abnormal lipid metabolism and silicosis, and is a potential therapeutic target for the treatment of silica-induced pulmonary fibrosis.

Inhibition of HIF-1α Attenuates Silica-Induced Pulmonary Fibrosis.

BACKGROUND: Excessive accumulation of extracellular matrix is a key feature of pulmonary fibrosis (PF), and myofibroblasts are the main producers of extracellular matrix. Fibroblasts are the major source of myofibroblasts, but the mechanisms of transdifferentiation are unclear. METHODS: In vitro, transforming growth factor-ß1 was used to induce NIH-3T3 cell transdifferentiation. DMOG was used to increase hypoxia-inducible factor-1α subunit (HIF-1α) expression. KC7F2 and siRNA decreased HIF-1α expression. In vivo, silica particles were used to induce PF in C57BL/6N mice, and KC7F2 was used to reduce HIF-1α expression in C57BL/6N mice. Western blot was used to detect the expression of collagen type 1 alpha 1(COL1A1), α-smooth muscle actin (α-SMA), SMAD family member (SAMD) 3, Phospho-SMAD3 (PSMAD3), and HIF-1α. PCR was used to detect the expression of COL1A1, α-SMA, and HIF-1α. Immunohistochemistry was used to detect the expression of COL1A1 and HIF-1α. RESULTS: In vitro, compared to the control group, COL1A1, α-SMA, PSMAD3, and HIF-1α expression were elevated in the DMOG group, and COL1A1, α-SMA, PSMAD3, and HIF-1α expression were decreased in the KC7F2 group and siRNA group. Compared to the DMOG group, COL1A1, α-SMA, and PSMAD3 expression were decreased in the DMOG + SIS3 group. In vivo, compared to the saline group, COL1A1, α-SMA, PSMAD3, and HIF-1α expression were increased in the pulmonary tissue of C57BL/6N mice in the silica group. Compared to the silica group, COL1A1, α-SMA, PSMAD3, and HIF-1α expression and the degree of PF were decreased in the silica + KC7F2 group. CONCLUSION: Inhibition of HIF-1α reduced α-SMA, decreased COL1A1 expression, and attenuated the degree of PF in C57BL/6N mice. Therefore, HIF-1α may be a new target for the treatment of silica-induced PF.

Effective Connectivity in Cortical Networks During Deception: A Lie Detection Study Based on EEG.

Thus far, when deception behaviors occur, the connectivity patterns and the communication between different brain areas remain largely unclear. In this study, the most important information flows (MIIFs) between different brain cortices during deception were explored. First, the guilty knowledge test protocol was employed, and 64 electrodes' electroencephalogram (EEG) signals were recorded from 30 subjects (15 guilty and 15 innocent). Cortical current density waveforms were then estimated on the 24 regions of interest (ROIs). Next, partial directed coherence (PDC), an effective connectivity (EC) analysis was applied in the cortical waveforms to obtain the brain EC networks for four bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz) and beta (13-30 Hz). Furthermore, using the graph theoretical analysis, the network parameters with significant differences in the EC network were extracted as features to identify the two groups. The high classification accuracy of the four bands demonstrated that the proposed method was suitable for lie detection. In addition, based on the optimal features in the classification mode, the brain "hub" regions were identified, and the MIIFs were significantly different between the guilty and innocent groups. Moreover, the fronto-parietal network was found to be most prominent among all MIIFs at the four bands. Furthermore, combining the neurophysiology significance of the four frequency bands, the roles of all MIIFs were analyzed, which could help us to uncover the underlying cognitive processes and mechanisms of deception.

PD-1/PD-L1 inhibitor ameliorates silica-induced pulmonary fibrosis by maintaining systemic immune homeostasis.

Pulmonary fibrosis induced by silica particles is defined as silicosis, which is an incurable disease. The pathogenesis of silicosis is not completely clear, but it's certain that immune system dysfunction is closely related to it. Immune checkpoint inhibitors (ICIs) are emerging immunotherapeutic agents that mainly target adaptive immune cells, and there is abundant evidence that ICIs are of great value in cancer treatment. However, whether these attractive agents can be implemented in silicosis treatment is unclear. In this study, we explored the efficacy of small molecule inhibitors targeted PD-1/PD-L1 and CTLA-4 on silica-induced pulmonary fibrosis in mice. ICIs were injected intraperitoneally into mice that received silica instillation twice a week. The mice were sacrificed 7 and 28 days after the injection. The lungs, spleen, hilar lymph nodes, thymus, and peripheral blood of mice were collected and subjected to histological examination, flow cytometry analysis, and mRNA and protein quantification. Our results demonstrated that silica exposure caused damage to multiple immune organs in mice, leading to an imbalance in systemic immune homeostasis. Specifically, proportions and subtypes of T and B cells were significantly altered, and the expressions of PD-1, PD-L1 and CTLA-4 were abnormal on these cells. Both PD-1/PD-L1 and CTLA-4 inhibitor administration modulated silica-induced immune system disruption, however, only PD-1/PD-L1 signaling inhibition showed significant amelioration of silicosis. Our findings confirmed for the first time the potential value of ICIs for the treatment of silica-induced pulmonary fibrosis, and this may provide new ideas for the treatment of other fibrosis-related diseases.

Research progress on the mechanism of ferroptosis and its clinical application.

Ferroptosis is a mode of cell death dependent on iron ions, which is mainly induced by the decrease of the biological activity of glutathione peroxidase or the accumulation of lipid peroxidation and reactive oxygen species (ROS). It is significantly different from autophagy and other forms of cell death in terms of cell morphology and biochemistry. The exact mechanisms of ferroptosis are not clear. More and more studies have shown that various tumor diseases and nervous system diseases are closely related to ferroptosis. The occurrence and development of related diseases can be tolerated by stimulating or inhibiting the occurrence of ferroptosis. Therefore, ferroptosis has occupied a very important position in recent years. This article reviews the discovery process, characteristics, mechanisms, inducers, inhibitors of ferroptosis and its related clinical applications to lay a foundation for follow-up researchers to study ferroptosis and provide some reference value.

Colorectal cancer occurrence and treatment based on changes in intestinal flora.

Colorectal cancer (CRC) is the most common cancer in the world, and its incidence has been increasing in recent years. The occurrence of CRC is believed to be related to a variety of factors. Epidemiological data indicate that CRC is mainly affected by environmental factors, eating habits, physical activity and genetic factors. As a newly recognized functional component, the intestinal microbiota plays important roles in preventing CRC formation and maintaining intestinal immunity. In this review, we summarize the mechanisms by which the gut microbiota causes CRC through alterations to immune function, focusing on the mechanisms by which intestinal microbial dysfunction promotes CRC. Furthermore, we describe the changes in the intestinal flora observed in CRC and their potential for CRC treatment with the goal of facilitating future research on the roles of the intestinal flora.

Deception Decreases Brain Complexity.

Extensive evidence suggests the feasibility of lie detection using electroencephalograms (EEGs). However, it is largely unknown whether there are any differences in the nonlinear features of EEGs between guilty and innocent subjects. In this study, we proposed a complexity-based method to distinguish lying from truth telling. A total of 35 participants were randomly divided into two groups, and their EEG signals were recorded with 14 electrodes. Averages for sequential sets of five trials were first calculated for the probe responses within each subject. Next, a common wavelet entropy (WE) measure and an improved one were used to quantify complexity from each five-trial average. The results show that for both measures, the WE values in the guilty subjects are statistically lower than those in the innocent subjects for most of the 14 electrodes. More importantly, using the improved measure, the difference in WE between the two groups of subjects significantly increases for 11 brain regions compared with the values from the common measure. Finally, the highest balanced classification accuracy, 89.64%, is achieved when using the combined WE feature vector in five brain regions from the sites of Pz, P3, C4, Cz, and C3. Our findings indicate that the lying task elicits a more ordered brain activity in some specific brain regions than the task of telling the truth. This study not only demonstrates that improved WE measurements could be a powerful quantitative index for detecting lying but also sheds light on the brain mechanisms underlying deceptive behaviors.