The changes and correlation of IL-6 and oxidative stress levels in RAW264.7 macrophage cells induced by PAHs in PM2.5.

The objective of this study was to investigate the effects of anthracene (Ant) with 3 rings, benzo[a]anthracene (BaA) with 4 rings and benzo[b]fluoranthene (BbF) with 5 rings in fine particulate matter (PM2.5) at different exposure times (4 h and 24 h) and low exposure levels (0 pg/mL, 0.1 pg/mL, 1 pg/mL, 100 pg/mL and 10,000 pg/mL) on RAW264.7 cells. The changes of interleukin-6 (IL-6) and oxidative stress levels in RAW264.7 cells were investigated by methyl-thiazolyl-tetrazolium (MTT) and enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to analyze the correlation between variables. Ant, BaA and BbF induced the secretion of IL-6 and the occurrence of oxidative stress in RAW264.7 cells. The inflammatory effect and oxidative damage were exacerbated with prolonged exposure time, increasing exposure concentration and increasing number of PAH rings. At the same time, IL-6 was found to have a certain correlation with the levels of ROS, MDA and SOD. Exposure to atmospheric PAHs at low concentrations can also produce toxic effects on cells, IL-6 and oxidative stress work together in cell damage. The study is expected to provide a theoretical and experimental basis for air pollution control and human health promotion.

A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine.

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.

Serum pro-surfactant protein B is correlated with clinical properties in osteosarcoma patients.

It is critical to find efficient non-invasive prognostic factor for osteosarcoma. In this study, we demonstrated that serum protein of pro-surfactant protein B (pro-SFTPB) may be a potential diagnostic indicator in osteosarcoma. We found that serum pro-SFTPB was highly expressed in osteosarcoma patients and presented good diagnostic value to discern osteosarcoma patients from non-osteosarcoma control subjects. Serum pro-SFTPB was also significantly correlated with advanced clinical stage, distant metastasis, and shorter overall survival. In addition, serum pro-SFTPB was demonstrated to be an independent prognostic factor for osteosarcoma. Overall, our study demonstrated that serum pro-SFTPB may be a useful diagnostic factor for osteosarcoma.

Constructing a prognostic risk model for Alzheimer's disease based on ferroptosis.

Introduction: The aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer's disease (AD) through gene expression changes. Methods: The GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aß1-42 on the expression profile of representative genes in vitro. Results: Based on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aß1-42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aß1-42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased. Discussion: The establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer's disease.

Epidemiological Analysis of Foodborne Botulism Outbreaks - China, 2004-2020.

Introduction: Foodborne botulism is a rare, potentially fatal illness resulting from the ingestion of foods contaminated with preformed botulinum neurotoxin types A, B, E, or F, produced by Clostridium botulinum. The descriptive epidemiology of foodborne botulism outbreaks in China during 2004-2020 was performed to inform public health response strategies. Methods: Data from 22 of 31 provincial-level administrative divisions (PLADs) of the National Foodborne Disease Outbreaks Surveillance System during 2004-2020 and Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Science and Technique Journals (CQVIP) from January 2004 to December 2020 to identify indexed publications in the Chinese literature using the following search terms "botulism," or "botulinum toxin," or "Clostridium botulinum." The number and proportion of outbreaks, illnesses, and deaths by PLAD, food types, and contributing factors were calculated. Results: During 2004-2020, a total of 80 foodborne botulism outbreaks occurred in China, involving 386 illnesses and 55 deaths; most outbreaks were reported between June and August, with a sharp peak in January; 22 out of 31 PLADs reported foodborne botulism outbreaks, Xinjiang reported the largest number of outbreaks (20), followed by Qinghai (13); the most commonly implicated foods were home-prepared traditional processed stinky tofu and dried beef, accounting for 51.25% events. Improper processing and improper storage in contributing factors accounted for 77.50% outbreaks. Initial misdiagnosis occurred in 27.50% of cases. Conclusions: Outbreaks of foodborne botulism had a high case-fatality rate. Targeted food safety and popularization education to farmers and herdsmen in Xinjiang and Qinghai related to botulism prevention should be carried out, and timely outbreak investigation and hospital surge capacity should be improved.

Stimulating the expression of sphingosine kinase 1 (SphK1) is beneficial to reduce acrylamide-induced nerve cell damage.

Sphingosine kinase 1 (SphK1) is an important signaling molecule for cell proliferation and survival. However, the role of SphK1 in acrylamide (ACR)-induced nerve injury remains unclear. The purpose of this study was to investigate the role and potential mechanism of SphK1 in ACR-induced nerve injury. Liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) and reverse transcription-quantitative PCR (RT-qPCR) were used to detect sphingosine 1-phosphate (S1P) content in serum and SphK1 content in whole blood from an occupational work group exposed to ACR compared to a non-exposed group. For in vitro experiments, SphK1 in human SH-SY5Y neuroblastoma cells was activated using SphK1-specific activator phorbol 12-myristate 13-acetate (PMA). Our research also utilized cell viability assays, flow cytometry, western blots, RT-qPCR and related protein detection to assess activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results of the population study showed that the contents of SphK1 and S1P in the ACR-exposed occupational contact group were lower than in the non-exposed group. The results of in vitro experiments showed that expression of SphK1 decreased with the increase in ACR concentration. Activating SphK1 improved the survival rate of SH-SY5Y cells and decreased the apoptosis rate. Activating SphK1 in SH-SY5Y cells also regulated MAPK signaling, including enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK) and inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and p38. These results suggest that activating SphK1 can protect against nerve cell damage caused by ACR.

T2 mapping for knee cartilage degeneration in young patients with mild symptoms.

BACKGROUND: We aimed to analyze the distribution of knee cartilage degeneration in young patients with mild symptoms using quantitative magnetic resonance imaging (MRI) T2 mapping. MATERIALS AND METHODS: This study included sixty six patients (case group) and twenty eight healthy volunteers (control group). The participants underwent 3.0 T conventional MRI plus a multi-echo sequence. The cartilage of each participant was divided into twenty eight subregions. We then calculated the T2 mean values and standard deviation or median and quartile range for each subregion according to whether the normal distribution was satisfied. Besides, we employed Kruskal-Wallis test to determine the statistical differences of each subregion in the control group while the Mann-Whitney U test was used to define the statistical difference between the case group and the control group and between the control group and subjects aged less than or equal to 35 years in the case group. RESULTS: In the case group, age of 30 male patients was 31.5 ± 9.3 and age of 36 female patients was 35.7 ± 8.3. In the two groups, the superficial central lateral femoral region exhibited relatively high T2 values (control/case group: 49.6 ± 2.7/55.9 ± 8.8), and the deep medial patellar region exhibited relatively low T2 values (control/case group: 34.2 ± 1.3/33.5(32.2, 35.5)). Comparison of the T2 values between the case and the control group demonstrated a statistically significant increase in nine subregions (P1 < 0.05) and there were five subregions in the case group with age ≤ 35 years (P2 < 0.05). In particular, the p-values for four subregions of the patellofemoral joint were all less than 0.05 (P1 = 0.002, 0.015, 0.036, 0.005). CONCLUSION: T2 values of patients were significantly different with values of healthy groups, especially in the superficial cartilage of the patellofemoral joint. It made T2 mapping helpful to early identify patients with knee cartilage degeneration.

Characteristics of Settings and Etiologic Agents of Foodborne Disease Outbreaks - China, 2020.

INTRODUCTION: Foodborne diseases are a growing public health problem and have caused a large burden of disease in China. This study analyzed epidemiological characteristics of foodborne diseases in China in 2020 to provide a scientific basis for prevention and control measures. METHODS: Data were collected from 30 of 31 provincial-level administrative divisions (PLADs) in the mainland of China, excluding Xizang (Tibet) Autonomous Region, via the National Foodborne Disease Outbreaks Surveillance System. The number and proportion of outbreaks, illnesses, hospitalizations, deaths by setting, pathogen-food category pairs and etiology were calculated. RESULTS: In 2020, 7,073 foodborne disease outbreaks were reported, resulting in 37,454 illnesses and 143 deaths. Among the identified pathogens, microbial pathogens were the most common confirmed etiology, accounting for 41.7% of illnesses. Poisonous mushrooms caused the largest proportion of outbreaks (58.0%) and deaths (57.6%). For venues where foodborne disease outbreaks occur, household had the highest number of outbreaks (4,140) and deaths (128), and catering service locations caused the largest proportion of illnesses (59.9%). Outbreaks occurring between June and September accounted for 62.8% of total outbreaks. CONCLUSIONS: Foodborne disease outbreaks mainly occurred in households. Microbial pathogens remained the top cause of outbreak-associated illnesses. Poisonous mushrooms were ranked the top cause of deaths in private homes in China. The supervision and management of food safety and health education should be strengthened to reduce the burden of foodborne diseases. Publicity should be increased to reduce the incidence of mushroom poisonings in families, and supervision and management of food should be strengthened to reduce microbial contamination.

Suppressive effects of human fetal keratinocytes on the proliferation, differentiation and extracellular matrix synthesis of human hypertrophic scar fibroblasts in vitro.

A hypertrophic scar is characterized by fibroblast proliferation and excessive extracellular matrix deposition. Emerging evidence has revealed that fetal keratinocytes (KCs) contribute to scarless wound healing. However, the association between fetal keratinocytesand hypertrophic scarring remains unclear. In the present study, human KCs of different gestational ages were isolated and co­cultured with human hypertrophic scar fibroblasts (HSFbs) or normal skin fibroblasts. Gene expression andprotein levels of fibronectin, collagen 1and α­smooth muscle actinin thefibroblasts were measured by reverse transcription­quantitative polymerase chain reaction and western blot analyses. It was observed that fetal KCs significantly inhibited the proliferation of HSFbs in vitro. Fetal keratinocytes also affected the expression of fibronectin, collagen 1and α­smooth muscle actin in HSFbs. In addition, miR­940 may modulate the suppressive effects of fetal KCson the cell proliferation, differentiation and extracellular matrix synthesis of HSFbs by directly targeting transforming growth factor­ß1. Taken together, the results of the present studyprovide evidence to support the potential use of fetal KCsfor cell­based therapeutic grafting in the prevention of hypertrophic scarring.

Antioxidants inhibit advanced glycosylation end-product-induced apoptosis by downregulation of miR-223 in human adipose tissue-derived stem cells.

Advanced glycosylation end products (AGEs) are endogenous inflammatory mediators that induce apoptosis of mesenchymal stem cells. A potential mechanism includes increased generation of reactive oxygen species (ROS). MicroRNA-223 (miR-223) is implicated in the regulation of cell growth and apoptosis in several cell types. Here, we tested the hypothesis that antioxidants N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) inhibit AGE-induced apoptosis via a microRNA-dependent mechanism in human adipose tissue-derived stem cells (ADSCs). Results showed that AGE-HSA enhanced apoptosis and caspase-3 activity in ADSCs. AGE-HSA also increased ROS generation and upregulated the expression of miR-223. Interestingly, reductions in ROS generation and apoptosis, and upregulation of miR-223 were found in ADSCs treated with antioxidants NAC and AAP. Furthermore, miR-223 mimics blocked antioxidant inhibition of AGE-induced apoptosis and ROS generation. Knockdown of miR-223 amplified the protective effects of antioxidants on apoptosis induced by AGE-HSA. miR-223 acted by targeting fibroblast growth factor receptor 2. These results indicate that NAC and AAP suppress AGE-HSA-induced apoptosis of ADSCs, possibly through downregulation of miR-223.

Effect of advanced glycosylation end products on apoptosis in human adipose tissue-derived stem cells in vitro.

BACKGROUND: Both apoptosis and caspase-3 activity in adipose tissue-derived stem cells play an important role in the therapeutic process of diabetes patients. The purpose of this study was to investigate the effect of advanced glycation end products-human serum albumin (AGE-HSA) on apoptosis in human adipose tissue-derived stem cells (ADSCs) and to characterize the signal transduction pathways activated by AGEs that are involved in apoptosis regulation. RESULTS: AGE-HSA promoted apoptosis and caspase-3 activity in ADSCs. However, the effects of AGE-HSA were significantly attenuated by an inhibitor of p38 MAPK, but not by inhibitors of JNK MAPK or ERK MAPK. AGE-HSA also upregulated the expression of RAGE. Silencing of the RAGE gene inhibited AGE-HSA-induced apoptosis, and activation and expression of phosphorylated p38 MAPK. CONCLUSIONS: These results suggest that AGE-HSA promote the apoptosis of ADSCs in vitro via a RAGE-dependent p38 MAPK pathway.

MicroRNA-21 promotes osteogenic differentiation by targeting small mothers against decapentaplegic 7.

Previous studies have suggested that microRNAs (miRNAs/miRs) may positively or negatively control osteogenic differentiation and mineralization by targeting negative regulators of osteogenesis or important osteogenic factors. miR-21 is important in osteoblast differentiation and Smad7 is a critical regulator of osteogenic differentiation, which inhibits proliferation, differentiation and mineralization in mouse osteoblast cells. However, the association between Smad7 and miR-21 remain to be elucidated. In the present study, miR-21 was found to promote the level of osteogenic differentiation and increase matrix mineralization in MC3T3-E1 cells. Furthermore, Smad7 was identified as a direct target of miR-21 in the MC3T3-E1 cells. The overexpression of miR-21 affected the protein levels of SMAD7, but not the mRNA levels, which suggested that miR-21 regulates the levels of SMAD7 by inhibiting translation, rather than by promoting mRNA decay. Forced expression of miR-21 promoted osteogenic differentiation and mineralization, while inhibition of miR-21 suppressed these processes. The present study also identified for the first time, to the best of our knowledge, the promotion of osteogenic differentiation and mineralization by miR-21, by repressing the expression of Smad7.

Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients.

In our study, we detect the levels of three micro-RNAs (miRNAs; miR-21, miR-133a and miR-146a) in the plasma of 120 Chinese postmenopausal women who were divided into three groups (normal, osteopenia and osteoporosis) according to the T-scores. Downregulation of miR-21, as well as upregulation of miR-133a, was validated in the plasma of osteoporosis and osteopenia patients versus the normal group. The difference in expression regarding the miR-146a level in plasma among the three groups was not significant (p > 0.01). The circulating miRNA expression levels and bone mineral density (BMD) were examined during a multiple correlation analysis as a dependent variable after adjusting for age, weight and height. We have demonstrated that specific miRNAs species are significantly changed in the plasma of osteoporosis and osteopenia patients and correlated with the BMD. Our study suggested a potential use of miR-21 and miR-133a as sensitive and plasma biomarkers for postmenopausal osteoporosis.

UNC5H4-induced apoptosis in non-small cell lung cancer is not dependent on p53 status only.

The aim of the present study was to investigate the expression profile and prognostic significance of uncoordinated 5 homolog 4 (UNC5H4) in patients with lung cancer and to evaluate whether UNC5H4 expression may serve as an index for radiosensitivity. UNC5H4 and p53 expression levels were detected by immunohistochemistry, apoptosis was determined by a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and caspase 3 activation was determined by western blotting. The results showed that UNC5H4 expression was largely located in the membrane of the normal bronchial epithelium, but absent in the membranous regions or ectopic cytoplasm of 80/130 (61.5%) non-small cell lung cancer (NSCLC) tissue samples. Abnormal UNC5H4 expression was demonstrated to correlate with the degree of differentiation (P=0.015), TNM staging (P=0.037). Cytoplasmic UNC5H4 expression was shown to correlate negatively with p53 mutant type (mt) expression (r=-0.270; P=0.002) and positively with the apoptotic index (r=0.254; P=0.004). The statistical analyses indicated that the prognosis of patients with normal UNC5H4 expression was improved compared with that of patients with abnormal UNC5H4 expression, however, no significant difference was identified (P=0.125). Exposure of NSCLC tissue samples to X-radiation increased UNC5H4 expression and caspase 3 activity significantly, irrespective of p53 mutation status. In conclusion, these results indicate that X-rays induce apoptosis via the p53 pathway, and when this pathway is compromised, an additional pathway is utilized.

[Diagnosis and treatment of testicular torsion in children].

OBJECTIVE: To explore the early diagnosis of testicular torsion in children. METHODS: The clinical data of 24 patients with testicular torsion were analyzed retrospectively. RESULTS: The patients ranged in age from 4 months to 15 years ( mean 10.3 years), 17 left and 7 right testes involved. The duration between the onset and operation varied from 1 hour to 4 months. Diagnoses were initially and correctly made in 16 cases and delayed in 8. Surgical explorations were carried out in 23 cases, and resection of the testis performed in 17. CONCLUSION: Testicular necrosis is associated not only with the duration and degree, but also with the extent of the torsion. Color Doppler has clinical value in the early diagnosis of child testicular torsion. Timely surgical exploration should be performed for cases of acute scrotal problem suspected of child testicular torsion.