Background Quartz dust cannot be degraded in the lungs, and inhalation of a large amount of quartz dust in the occupational production process will lead to the occurrence of pulmonary fibrosis, and then develop into silicosis. In recent years, studies have found that exosomes may be involved in the pathogenesis of fibrotic diseases by carrying microribonucleic acid (miRNA), but the mechanism of their actions in silicosis still needs to be studied. Objective To investigate the role of exosome-derived miRNA-21-5p/mothers against decapentaplegic homolog 7 (Smad7) in quartz dust-induced pulmonary fibrosis in rats. Methods Twenty-four healthy male SD rats were randomly divided into four groups (six rats in each group): control 4-week group, control 16-week group, quartz 4-week group, and quartz 16-week group. At the beginning of the experiment, 1 mL of quartz suspension (50 mg·mL⁻¹) and 1 mL of normal saline were injected into the trachea of rats in the quartz group and the control group, respectively, by means of one-time non-exposure intratracheal dust staining. Alveolar lavage was performed at the 4th and 16th weeks after dust staining, the exosomes in lavage solution were extracted by polyethylene glycol (PEG) precipitation, morphological identification was conducted by transmission electron microscopy (TEM), particle size of exosomes was detected by nano-tracking analysis (NTA), and the marker proteins CD9 and CD63 of exosomes were detected by Western blotting (WB). The expression of miRNA-21-5p in exosomes was determined by reverse transcription polymerase chain reaction (RT-PCR). The degree of lung tissue injury and fibrosis was observed by hematoxylin-eosin staining (HE) and Masson staining. The collagen content of lung tissue was detected by hydroxyproline (HYP) method. The expression of Smad7 protein in lung tissue was detected by WB. Results The results of pathological staining showed that compared with the control group, lung inflammatory cell infiltration, alveolar wall thickening, and collagen increase were observed after 4 weeks of dusting, and collagen deposition and silicon nodules appeared after 16 weeks of dusting. Compared with the control group, the expression level of HYP in the lung tissue of the quartz group was increased after 4 weeks and 16 weeks of dust staining (P<0.05). Transmission electron microscopy showed that exosomes were saucer-shaped, and the average particle size of exosomes was 95.8 nm by NTA. Positive expression of exosome marker proteins CD9 and CD81 was found by WB. Compared with the control group, the expression of exosome-derived miRNA-21-5p in alveolar lavage fluid in the quartz group increased in the 4th week and the 16th week (P<0.05), and the expression of Smad7 protein in lung tissue decreased (P<0.05). Conclusion Exosome-derived miRNA-21-5p and Smad7 may be involved in the mechanism of quartz dust-induced pulmonary fibrosis in rats.

Objective: To explore the effects of subchronic aluminum exposure on the level of N6-methyladenosine (m6A) methylation and the expression of N6-methyladenosine RNA binding protein 1 (YTHDF1) in the hippocampus of rats. Methods: Twenty-four healthy male SD rats were randomly divided into the control group (normal saline), the low dose group [10 μmol/kg Al(mal)3], the medium dose group [20 μmol/kg Al(mal)3] and the high dose group [40 μmol/kg Al(mal)3], with 6 rats in each group. The Al(mal)3 solution was administered via intraperitoneal injection on alternate days for 90 days. Escape latency, target quadrant dwell time and platform crossing times were tested to evaluate the learning and memory ability of the rats by the Morris water maze test after exposure. The brain tissue was weighted and the brain-to-body weight ratio was calculated after euthanasia. The level of m6A methylation and the expression of YTHDF1 were determined by enzyme-linked immunosorbent assay and western blot assay, respectively. Results: All rats survived during aluminum exposure period. The brain-to-body weight ratios of the control group and the low, medium and high dose groups were (0.46±0.06)%, (0.44±0.04)%, (0.49±0.06)% and (0.51±0.07)%, respectively, with no statistically significant differences (P>0.05). The escape latency of rats in the high dose group was longer than that in control and low group during the third to fifth day (both P>0.05). The escape latency of rats in all groups was shortened with the increase of training days (P<0.05). The target quadrant dwell time of rats in low, medium and high dose groups were lower than that in control group, and the platform crossing times of rats in high dose group were lower than that in control group (all P<0.05). The methylation level of m6A and expression level of YTHDF1 in hippocampus of rats in medium and high dose groups was higher than that in control group (both P<0.05). Conclusion The learning and memory impairment caused by subchronic aluminum exposure may be related to the increase of m6A methylation level and the decrease of YTHDF1 expression.

Objective To investigate the protective effect of thalidomide on acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats and its possible mechanism. Methods Sixty SPF Wistar rats were randomly divided into six groups with 10 rats in each group. The rat model of PQ poisoning was reproduced by intraperitoneal injection of PQ solution 20 mg/kg (PQ model group), and the rats were treated by intraperitoneal injection of gradient thalidomide (50, 100, 200 mg/kg treatment groups) 30 minutes later continuously for 3 days. The normal saline (NS) control group and thalidomide control group (thalidomide 200 mg/kg) were established. After 3 days, the abdominal aorta blood was collected, and the superoxide dismutase (SOD) activity was determined by hydroxylamine method, serum malondialdehyde (MDA) content was determined by thiobarbituric acid method. The rats were sacrificed for lung tissue, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). The phosphorylation levels of p65 and inhibitor-α of nuclear factor-κB (NF-κB) (IκB-α), which were the NF-κB signaling pathway proteins, were determined by Western Blot. The pathological changes in lung tissue were observed under light microscope by hematoxylin-eosin (HE) staining. Results Under microscope, obvious congestion of pulmonary interstitial and alveolar septum, a large number of inflammatory cells infiltration and thickened alveolar wall were observed after 3 days of PQ poisoning, and the congestion of pulmonary interstitial and alveolar septum, edema and inflammatory cells infiltration in the lung tissue were significantly reduced after treatment of 50, 100, 200 mg/kg thalidomide, but compared with NS control group, there was still a small amount of edema fluid, inflammatory cells and erythrocytes in the lungs tissue. Compared with the NS control group, serum MDA content and the levels of TNF-α and IL-6, and the phosphorylation of p65 and IκB-α in lung tissue were significantly increased after PQ exposure, and the activity of serum SOD was significantly decreased. Treatment with 50, 100, 200 mg/kg thalidomide could significantly reduce the levels of MDA, TNF-α, IL-6, and phosphorylation of IκB-α and p65, and increase SOD activity, in a dose-dependent manner, and the levels were significantly different from PQ model group [MDA (mmol/L): 8.26±1.20, 6.72±1.18, 5.51±1.44 vs. 9.02±1.03, TNF-α (ng/mg): 3.00±0.14, 1.84±0.18, 1.58±0.11 vs. 3.30±0.14, IL-6 (ng/mg): 1.26±0.04, 1.06±0.04, 0.97±0.08 vs. 1.97±0.07, p-p65/p65: 6.01±0.35, 3.64±0.15, 2.89±0.18 vs. 6.34±0.23, p-IκB-α/IκB-α: 2.27±0.13, 2.14±0.22, 1.52±0.14 vs. 2.96±0.20, SOD (kU/L): 195.7±19.3, 207.1±25.6, 225.8±23.1 vs. 188.2±26.6, all P < 0.05]. There was no significant effect on lung by 200 mg/kg thalidomide alone. Conclusion Thalidomide has a protective effect on ALI induced by PQ poisoning in rats in a dose-dependent manner, the mechanism may be achieved by reducing the level of oxygen free radicals, reducing the inflammatory factor and inhibiting the IκB-α/NF-κB signal pathway activation.

Background Chemical modification of RNA is a recent hotspot in the field of epigenetics, but the specific mechanism of chemical modification of RNA in aluminum neurotoxicity has not been fully reported. Objective To investigate the alterations of fat mass and obesity-associated protein (FTO), that demethylates N6-methyladenosine (m⁶A), and brain-derived neurotrophic factor (BDNF) in different brain regions of rats and rat adrenal pheochromocytoma differentiated cells (PC12 cells) following aluminum exposure. Methods Animal experiment: Twenty-four healthy male SD rats were randomly divided into a control group (normal saline) and 10, 20, and 40 μmol·kg⁻¹ exposure groups according to body weight, with 6 rats in each group. Maltol aluminum [Al(mal)₃] was injected intraperitoneally every other day for 3 months. Cell experiment: PC12 cells were divided into a control group and 100, 200, and 400 μmol·L⁻¹ exposure groups exposed to Al(mal)₃ for 24 h. After exposure, the learning and memory ability of rats was measured by water maze experiment, and the protein expression levels of FTO and BDNF in rat cortex (n=6) and hippocampus (n=6) samples as well as in PC12 cells (n=5) were determined by Western blotting. Results The results of water maze test showed that the escape latency of the 40 μmol·kg⁻¹Al(mal)₃ group was higher than those of the control group, the 10 μmol·kg⁻¹Al(mal)₃ group, and the 20 μmol·kg⁻¹Al(mal)₃ group on day 3, 4, and 5 of training (P<0.05). The retention time of the target quadrant of the 40 μmol·kg⁻¹Al(mal)₃ group was also reduced compared with that of the control group (P<0.05), indicating that aluminum exposure damaged the learning and memory ability of the rats. The Western blotting results showed that in the cortex, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05). In the hippocampus, compared with the control group, the protein expression levels of FTO and BDNF in the 20 μmol·kg⁻¹ and the 40 μmol·kg⁻¹Al(mal)₃ groups were decreased (P<0.05). In PC12 cells, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05). Conclusion Aluminum-induced learning and memory impairment is related to a simultaneous reduction of FTO and BDNF protein expressions, suggesting that m⁶A methylation may be involved.

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.
Humans ; Carcinoma, Squamous Cell/therapy* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/therapy* ; Head and Neck Neoplasms ; Tumor Microenvironment