Polychlorinated biphenyls (PCBs) are notorious environmental pollutants. For their hydrophobic and lipophilic capability, they are wildly spread to environment to threat human health thus attracts more attention. In this study, we observed increasing numbers of CD163 positive (CD163⁺) macrophages in aortic valve of ApoE⁻/⁻ mice after 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ) treatment, the metabolite of polychlorinated biphenyl. In addition, in vitro studies identified that PCB29-pQ exposure significantly provoked the shifting of RAW264.7 macrophages and bone marrow derived monocytes (BMDMs) to CD163⁺ macrophages. Upon PCB29-pQ administration, CD163 and CD206 levels were enhanced in RAW264.7 cells as well as in BMDMs. However, the concentration of iron and total cholesterol (TC) were reduced due to the boosting of ferroportin (Fpn) and ATP binding cassette transporter, subfamily A, member 1 (ABCA1) which are efflux transporters of iron and cholesterol individually. Further investigation on mechanism indicated that PCB29-pQ exposure induced reactive oxygen species (ROS), which may result in activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a protein responsible for macrophage polarization. After that, we blocked Nrf2 through Nrf2 shRNA and ROS scavenger NAC, which significantly reversed the shifting of macrophage to CD163⁺ sub-population. These results confirmed the importance of Nrf2 in inducing macrophage polarization. In short, our study uncovered that PCB29-pQ could promote macrophage/monocyte polarization to CD163⁺ macrophage which would be a potential incentive to accelerate atherosclerosis through Nrf2 signaling pathway.

Exposure to fine atmospheric Particulate Matter (PM) is one of the major environmental causes involved in the development of inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD) or asthma. When PM is penetrating in the pulmonary system, alveolar macrophages represent the first line of defense, in particular by triggering a pro-inflammatory response, and also by their ability to recruit infiltrating macrophages from the bone marrow. The aim of this in vitro study was to evaluate the gene expression and cytokine production involved in the toxicological and inflammatory responses of infiltrating macrophages, as well as the Extracellular Vesicles (EVs) production, after their exposure to PM. The ability of these EVs to convey information related to PM exposure from exposed macrophages to pulmonary epithelial cells was also evaluated.Infiltrating macrophages respond to fine particles exposure in a conventional manner, as their exposure to PM induced the expression of Xenobiotic Metabolizing Enzymes (XMEs) such as CYP1A1 and CYP1B1, the enzymes involved in oxidative stress SOD2, NQO1 and HMOX as well as pro-inflammatory cytokines in a dose-dependent manner. Exposure to PM also induced a greater release of EVs in a dose-dependent manner. In addition, the produced EVs were able to induce a pro-inflammatory phenotype on pulmonary epithelial cells, with the induction of the release of IL6 and TNFα proinflammatory cytokines. These results suggest that infiltrating macrophages participate in the pro-inflammatory response induced by PM exposure and that EVs could be involved in this mechanism.

Humans benefit from nuclear technologies but consequently experience nuclear disasters or side effects of iatrogenic radiation. Hematopoietic system injury first arises upon radiation exposure. As an intricate new layer of genetic control, the posttranscriptional m⁶A modification of RNA has recently come under investigation and has been demonstrated to play pivotal roles in multiple physiological and pathological processes. However, how the m⁶A methylome functions in the hematopoietic system after irradiation remains ambiguous. Here, we uncovered the time-varying epitranscriptome-wide m⁶A methylome and transcriptome alterations in γ-ray-exposed mouse bone marrow. 4 Gy γ-irradiation rapidly (5 min and 2 h) and severely impaired the mouse hematopoietic system, including spleen and thymus weight, blood components, tissue inflammation and malondialdehyde (MDA) levels. The m⁶A content and expression of m⁶A related enzymes were altered. Gamma-irradiation triggered dynamic and reversible m⁶A modification profiles and altered mRNA expression, where both m⁶A fold-enrichment and mRNA expression most followed the (5 min_up/2 h_down) pattern. The CDS enrichment region preferentially upregulated m⁶A peaks at 5 min. Moreover, the main GO and KEGG pathways were closely related to metabolism and the classical radiation response. Finally, m⁶A modifications correlated with transcriptional regulation of genes in multiple aspects. Blocking the expression of m⁶A demethylases FTO and ALKBH5 mitigated radiation hematopoietic toxicity. Together, our findings present the comprehensive landscape of mRNA m⁶A methylation in the mouse hematopoietic system in response to γ-irradiation, shedding light on the significance of m⁶A modifications in mammalian radiobiology. Regulation of the epitranscriptome may be exploited as a strategy against radiation damage.

As alternatives to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA) have raised concerns of their potential health risks. Human bone marrow mesenchymal stem cell was employed as an in vitro model to investigate the molecular targets and the adverse effects of HFPOs in stem cells in concentrations range starting at human relevant levels. Unsupervised transcriptomic analysis identified 1794 and 1429 DEGs affected by HFPO-TA and HFPO-DA, respectively. Cell cycle-associated biological processes were commonly altered by both chemicals. 18 and 35 KEGG pathways were enriched in HFPO-TA and HFPO-DA treatment group, respectively, among which multiple pathways were related to cancer and pluripotency. Few genes in PPAR signalling pathway were disturbed by HFPOs suggesting the involvement of PPAR-independent toxic mechanism. HFPO-TA promoted cell proliferation with significance at 1 μM mRNA levels of CDK and MYC were down-regulated by HFPOs, suggesting the negative feedback regulation to the abnormal cell proliferation. Decreased expression of CD44 protein, and ENG and THY1 mRNA levels demonstrated HFPOs-caused changes of hBMSCs phenotype. The osteogenic differentiation was also inhibited by HFPOs with reduced formation of calcium deposition. Furthermore, gene and protein expression of core pluripotency regulators NANOG was enhanced by HFPO-TA. The present study provides human relevant mechanistic evidence for health risk assessment of HFPOs, prioritizing comprehensive carcinogenicity assessment of this type of PFOA alternatives.

Cadmium (Cd) is a heavy metal toxicant as a common pollutant derived from many agricultural and industrial sources. The absorption of Cd takes place primarily through Cd-contaminated food and water and, to a significant extent, via inhalation of Cd-contaminated air and cigarette smoking. Epidemiological data suggest that occupational or environmental exposure to Cd increases the health risk for osteoporosis and spontaneous fracture such as itai-itai disease. However, the direct effects and underlying mechanism(s) of Cd exposure on bone damage are largely unknown. We used primary bone marrow-derived mesenchymal stromal cells (BMMSCs) and found that Cd significantly induced BMMSC cellular senescence through over-activation of NF-κB signaling pathway. Increased cell senescence was determined by production of senescence-associated secretory phenotype (SASP), cell cycle arrest and upregulation of p21/p53/p16ᴵᴺᴷ⁴ᵃ protein expression. Additionally, Cd impaired osteogenic differentiation and increased adipogenesis of BMMSCs, and significantly induced cellular senescence-associated defects such as mitochondrial dysfunction and DNA damage. Sprague-Dawley (SD) rats were chronically exposed to Cd to verify that Cd significantly increased adipocyte number, and decreased mineralization tissues of bone marrow in vivo. Interestingly, we observed that Cd exposure remarkably retarded bone repair and regeneration after operation of skull defect. Notably, pretreatment of melatonin is able to partially prevent Cd-induced some senescence-associated defects of BMMSCs including mitochondrial dysfunction and DNA damage. Although Cd activated mammalian target of rapamycin (mTOR) pathway, rapamycin only partially ameliorated Cd-induced cell apoptosis rather than cellular senescence phenotypes of BMMSCs. In addition, a selective NF-κB inhibitor moderately alleviated Cd-caused the senescence-related defects of the BMMSCs. The study shed light on the action and mechanism of Cd on osteoporosis and bone ageing, and may provide a novel option to ameliorate the harmful effects of Cd exposure.

Recently, bio-nanofabrication becomes one of the widest methods for synthesizing nanoparticles (NPs); however, there is scanty literature exploring the toxicity of these green NPs against living organisms. This study aimed to evaluate the potential protective role of encapsulated cinnamon oil (ECO) against titanium oxide nanoparticle (TiO₂NP)–induced oxidative stress, DNA damage, chromosomal aberration, and reproductive disturbances in male mice. Sixty male Balb/c mice were distributed into six groups treated orally for 3 weeks and included control group, TiO₂NP-treated group (25 mg/kg b.w), ECO at low or high dose–treated groups (50 or 100 mg/kg b.w), and the groups that received TiO₂NPs plus ECO at a low or high dose. The results of GC-MS revealed the isolation of 21 compounds and the majority was cinnamaldehyde. The average size zeta potential of TiO₂NPs and ECO were 28.9 and 321 nm and −33.97 and −17.35 mV, respectively. TiO₂NP administration induced significant changes in liver and kidney function, decreased antioxidant capacity, and increased oxidative stress markers in liver and kidney, DNA damage in the hepatocytes, the number of chromosomal aberrations in the bone marrow and germ cells, and sperm abnormalities along with histological changes in the liver, kidney, and testis. Co-administration of TiO₂NPs and ECO could alleviate these disturbances in a dose-dependent manner. It could be concluded that ECO is a promising and safe candidate for the protection against the health hazards of TiO₂NPs.

The adverse health effects of benzene occupational and circumstance pollution exposure are an increasing concern. It leads to damage to various human tissues including bone marrow and ovarian tissues and many vital physiological processes. Previous studies showed that kefir is a rich probiotic, having protective effect, thanks to its antioxidant, anti-inflammatory, and immunomodulatory capacity. The purpose of this study was to evaluate the potential efficacy of kefir to remediate benzene toxicity in rat. Thirty-two female rats were randomly allocated and administered orally with benzene and/or kefir during a period of 21 consecutive days. At the end of the experiment, hematological and bone marrow cell changes were estimated. The animals exposed to benzene exhibited anemia and a significant decrease in the levels of white blood cell. Moreover, benzene led to the activation of gene expression of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), a myelotoxicity in bone marrow cells. Our data showed that kefir treatment alleviated benzene-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in the bone marrow. Furthermore, these physiological results were observed with animals showing high concentrations of lactic acid bacteria (LAB) determined from fecal samples, which are considered an indicator of kefir-associated microorganisms. Our study suggests that kefir is a potential nutritional supplement target to attenuate hematotoxicity induced by benzene.

Glyphosate-based herbicides (GBH) are the most widely used herbicide for treatment of crops in the world. The digestive tract is one of the first systems exposed to pesticides, and damage to this system can affect the general health of individuals. The aim of this study was to evaluate the effects of subchronic inhalation and oral exposure to GBH on the digestive tract in rats. Six groups of Wistar rats (male and female) were exposed to nebulization with three concentrations of GBH [3.71 × 10⁻³ grams of active ingredient per hectare (g.a.i./ha), 6.19 × 10⁻³ g.a.i./ha and 9.28 × 10⁻³ g.a.i./ha] administered orally or by inhalation for 75 days. Bone marrow cells, smears of the tongue and fragments of the tongue, oesophagus, stomach and intestine were collected for histopathological analysis. Congestion, inflammation, an increase in the number of mast cells and nucleoli-organizing regions were detected in the tongue in the groups exposed to GBH. Females had a higher number of mast cells in the tongue than males. Animals in the groups exposed to higher concentrations of GBH showed dysplasia in the oesophagus and small and large intestine regardless of sex. Gastric changes were not observed. Animals exposed to GBH showed increased micronucleus formation. Our data indicate that GBH causes oral allergies and dysplastic lesions in the oesophagus and small and large intestine and has genotoxic potential.

The role of chemical elements in an organism is versatile and multifunctional. However, you should pay attention to the reaction of the organism on the introduction of chemical elements with different biological roles, which is predetermined by the physiological role of organs and body systems. These include the red bone marrow, which primarily responds to endogenous and exogenous factors by its functional significance. Analyzing the myelogram of birds after the various ways of copper NP introduction into the body and the different dosages, we found that, by the end of the experiment, the total numbers of bone marrow cells in all groups were lower than the initial values: in the second group—12.54% lower (p < 0.05), in third—26.32% lower (p < 0.001), for the fourth—14.75% lower (p < 0.05), with exception for the first experimental group where this index was 45.51% higher (р < 0.001). We revealed the following changes in the peripheral blood: the hemoglobin content by the end of the experiment was significantly higher than the initial values: by 18.63% for the first group (p < 0.01); 28.61% higher in the third group (p < 0.001); and 15.76% higher for the fourth (p < 0.01), except the animals of the second group (3.23% lower). The concentration of erythrocytes in all groups was higher than that of the background: by 24.56% (p < 0.001), by 3.37%, by 26.18% (p < 0.001), and by 14.85% (p < 0.01), respectively; the leukocyte concentration in the first group was 39.63% higher (p < 0.001), it remained at the level of the initial values in the other groups. The erythrocyte sedimentation rate in all groups increased by 2.4, 4.0, 2.01, and 1.86 times (p < 0.001), respectively. We revealed that the introduction of copper into an organism in the form of nanopowder both with feed and intramuscularly significantly caused an increase of the content of such elements as arsenic, copper, and silicon and a decrease of calcium, potassium, magnesium, phosphorus, boron, cobalt, iodine, lithium, sodium, zinc, tin, and strontium in the marrowy aspirate. Moreover, compared with the first group (p < 0.01), increasing doses of nanopowders caused a significant rise in the arsenic and tin concentrations and a decline of iodine and strontium. We found that copper nanoparticles ambiguously affect the bone marrow hemopoiesis of poultry; increasing the dose and changing the type of introduction activating the bone marrow hematopoietic function, in particular, granulocyto-, megakaryocyto-, and erythropoiesis.

Nigella sativa oil (NSO) possesses antioxidant activity. However, its protective role against the hazards of fungicides has been poorly studied. Therefore, the present work aimed at determining the ameliorative potential of NSO against hepatotoxicity induced by carbendazim (CBZ) and/or mancozeb (MNZ) in female rats. In the present study, about 120 adult female Sprague-Dawley rats were randomly divided into eight equal groups. One group of animals was kept as a negative control (Gp. 1); groups 2, 3 and 4 orally received CBZ (200 mg/kg body wt) and/or MNZ (300 mg/kg body wt) daily for 2 weeks (positive groups). In order to assess the hepatoprotective potential of NSO, in comparison with NSO-treated rats (Gp. 5), groups 6, 7 and 8 were CBZ- and/or MNZ-exposed groups pre-treated orally with NSO (2 ml/kg body wt) daily for 2 weeks (prophylactic groups). All groups were kept further for 15 days without medications to observe the withdrawal effect. At the end of exposure and withdrawal periods, the body weight of all experimental rats was recorded and blood samples were collected for hematological, clinico-biochemical, and micronucleus assays. The animals were then sacrificed, and the liver and bone marrow were harvested for oxidative stress bioassay, chromosomal aberrations, DNA fragmentation, and histopathological examinations. The results suggested that pre-treatment with NSO remarkably diminished CBZ- and MNZ-induced macrocytic hypochromic anemia, leukocytosis, lymphocytosis, eosinophilia, and neutropenia. Besides, it also minimized the elevated liver enzymes, lipid peroxidation, micronucleus incidence, DNA damage, and chromosomal aberration frequency. Conversely, NSO significantly stimulated the CBZ- and/or MNZ-induced antioxidant system suppression. The NSO also normalized the hepatic structural architecture. As far as withdrawal effect is concerned, there was almost disappearance of the bad effects of these fungicides and the values were close to the normal range especially with the use of NSO. Ultimately, the results revealed that N. sativa oil is an effective hepatoprotective agent due to its genoprotective and free radical scavenging activities.