The mediation effect of asprosin on the association between ambient air pollution and diabetes mellitus in the elderly population in Taiyuan, China.

Evidence around the relationship between air pollution and the development of diabetes mellitus (DM) remains limited and inconsistent. To investigate the potential mediation effect of asprosin on the association between fine particulate matter (PM2.5), tropospheric ozone (O3) and blood glucose homeostasis. A case-control study was conducted on a total of 320 individuals aged over 60 years, including both diabetic and non-diabetic individuals, from six communities in Taiyuan, China, from July to September 2021. Generalized linear models (GLMs) suggested that short-term exposure to PM2.5 was associated with elevated fasting blood glucose (FBG), insulin resistance index (HOMA-IR), as well as reduced pancreatic ß-cell function index (HOMA-ß), and short-term exposure to O3 was associated with increased FBG and decreased HOMA-ß in the total population and elderly diabetic patients. Mediation analysis showed that asprosin played a mediating role in the relationship of PM2.5 and O3 with FBG, with mediating ratios of 10.2% and 18.4%, respectively. Our study provides emerging evidence supporting that asprosin mediates the short-term effects of exposure to PM2.5 and O3 on elevated FBG levels in an elderly population. Additionally, the elderly who are diabetic, over 70 years, and BMI over 24 kg/m2 are more vulnerable to air pollutants and need additional protection to reduce their exposure to air pollution.

PM2.5-bound metals and blood metals are associated with pulmonary function and Th17/Treg imbalance: A panel study of asthmatic adults.

Growing research has demonstrated that exposure to fine particulate matter (PM2.5) was associated with decreased pulmonary function and obvious inflammatory response. However, few pieces of research focus on the effects of PM2.5-bound metals on people with asthma. Here, we assessed whether PM2.5 and PM2.5-bound metals exposure could worsen pulmonary function in asthmatic patients and further elucidate the possible mechanisms. Thirty-four asthmatic patients were recruited to follow up for one year with eight visits in 2019-2020 in Taiyuan City, China. The index of pulmonary function was detected and blood and nasal epithelial lining fluid (ELF) samples were acquired for biomarkers measurement at each follow-up. Linear mixed-effect (LME) models were used to evaluate the relations between PM2.5, PM2.5-bound metals, and blood metals with lung function and biomarkers of Th17/Treg balance. The individual PM2.5 exposure concentration varied from 37 µg/m3 to 194 µg/m3 (mean: 59.63 µg/m3) in the present study. An interquartile range (IQR) increment of PM2.5 total mass was associated with a faster decline in maximal mid-expiratory flow (MMEF) and higher interleukin-23 (IL-23). PM2.5-bound metals [e.g. copper (Cu), nickel (Ni), manganese (Mn), titanium (Ti), and zinc (Zn)] were significantly associated with IL-23 (Cu: 5.1126%, 95% CI: 9.3708, 0.8544; Mn: 14.7212%, 95% CI: 27.926, 1.5164; Ni: 1.0269%, 95% CI: 2.0273, 0.0264; Ti: 16.7536%, 95% CI: 31.6203, 1.8869; Zn: 24.5806%, 95% CI: 46.609, 2.5522). Meanwhile, blood lead (Pb) and Cu were associated with significant declines of 0.382-3.895% in MMEF and maximum ventilatory volume (MVV). Blood Pb was associated with descending transforming growth factor ß (TGF-ß). In conclusion, exposure to PM2.5-bound metals and blood metals is a risk factor for decreased pulmonary function, especially in small airways. These alterations might be partially attributed to the imbalance of Th17/Treg.

Lycopene attenuates D-galactose-induced cognitive decline by enhancing mitochondrial function and improving insulin signaling in the brains of female CD-1 mice.

The incidence of neurodegenerative diseases is severely increasing with ageing. Lycopene (LYC), a carotenoid pigment, has been reported to have antioxidant, anti-inflammatory and neuroprotective properties. In the present study, we aimed to investigate the ameliorative effect of LYC on D-galactose (D-gal) induced cognitive defects and the underlying mechanisms. Forty-five female CD-1 mice (2 months old) were separated into three groups to be fed with either a normal diet or a LYC diet (0.03%, w/w, mixed into normal diet). Meanwhile, the mice were treated by intraperitoneal injection of normal saline or D-gal 150 mg/kg/day for 8 weeks. The behavioral test results indicated that LYC alleviated D-gal induced cognitive impairments. LYC ameliorated brain ageing by decreasing the number of SA-ß-gal- stained neurons, downregulating the protein expression of the cellular senescence associated genes P19/P21/P53, increasing the activities of the antioxidant enzymes GSH and SOD, downregulating the level of ROS, inhibiting the activation of MAPKs signaling and downregulating the levels of the inflammatory cytokines IL-1ß and TNFɑ in mouse brains. LYC ameliorated synaptic dysfunction by increasing the expression of the neurotrophic factor BDNF and synaptic proteins. Moreover, LYC attenuated D-gal-induced mitochondrial morphological damage, and promoted the expression of mitochondrial functional proteins. LYC also promoted insulin signal transduction in mouse brains through the regulation of IRS-1/AKT/GSK3ß signaling.

Lycopene attenuates oxidative stress-induced hepatic dysfunction of insulin signal transduction: involvement of FGF21 and mitochondria.

Lycopene (LYC) has been regarded as a nutraceutical that has powerful antioxidant and hepatoprotective bioactivities. In the present study, we aimed to investigate the beneficial effects of LYC on hepatic insulin signal transduction under oxidative stress conditions and the possible involvement of FGF21 and mitochondria pathways. Two-month-old CD-1 mice were treated by intraperitoneal injection of D-galactose (D-gal) 150 mg/kg/day for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC increased the expression of FGF21, alleviated mitochondrial dysfunction and improved hepatic insulin signal transduction in D-gal-treated mice. Furthermore, knockdown of FGF21 by small interfering RNA notably suppressed mitochondrial function and blunted LYC-stimulated insulin signal transduction in H2O2-treated HepG2 cells. Moreover, suppressed mitochondrial function via oligomycin also inhibited insulin signal transduction, indicating that LYC supplementation ameliorated oxidative stress-induced hepatic dysfunction of insulin signal transduction by up-regulating FGF21 and enhancing mitochondrial function.

Lycopene attenuates D-galactose-induced insulin signaling impairment by enhancing mitochondrial function and suppressing the oxidative stress/inflammatory response in mouse kidneys and livers.

Lycopene (LYC) possesses bioactivity to improve the pathogenesis of several chronic diseases via antioxidant-associated mechanisms. The purpose of this study was to investigate whether LYC could attenuate D-galactose (D-gal)-induced mitochondrial dysfunction and insulin signaling impairment in mouse kidneys and livers. Two-month-old CD-1 mice were treated by intraperitoneal injection of 150 mg kg-1 day-1D-gal for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC ameliorated oxidative stress triggered by D-gal by enhancing the Nrf2 antioxidant defense pathway and increasing the expression of the antioxidant response genes HO-1 and NQO1 in mouse kidneys and livers. LYC inhibited the MAPK and NFκB pathways and attenuated renal and hepatic inflammatory responses. Moreover, LYC upregulated the expression of genes related to mitochondrial biosynthesis and oxidative phosphorylation and improved insulin signal transduction through the IRS-1/AKT/GSK3ß pathway in mouse kidneys and livers.

The cardiotoxicity of asthmatic rats after traffic-related PM2.5 and water-soluble components exposure mediated by endoplasmic reticulum stress and autophagy.

Fine particulate matter (PM2.5) is closely related to cardiopulmonary diseases; it is known that the respiratory system is related to the cardiovascular system. This study aimed to investigate the toxic effects of traffic-related PM2.5 (TRPM2.5) and water-soluble components (WSC) on hearts of asthmatic rats and explore potential molecular mechanisms. Here, ovalbumin (OVA)-sensitized asthmatic rats were intratracheally instilled with TRPM2.5 and WSC every 3 days in total of eight times. Significant myocardial pathological changes were observed in the TRPM2.5 and WSC group by hematoxylin-eosin (HE) staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) results demonstrated TRPM2.5 and WSC aggravated apoptosis of myocardial cells, which may be triggered by endoplasmic reticulum stress (ERS), as manifested by elevated GRP78, CHOP, and caspase-12. Likewise, TRPM2.5 and WSC activated autophagy via upregulation of LC3 and p62 gene and protein expression. In conclusion, TRPM2.5 and WSC may aggravate heart injury in asthmatic rats, possibly through the activation of ERS and autophagy signaling pathway.

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis.

Nonalcoholic fatty liver disease (NAFLD) is becoming more common in the world and is presenting a great challenge concerning prevention and treatment. Plant sterol ester of α-linolenic acid (PS-ALA) has a potential benefit to NAFLD. To examine the effect of PS-ALA on NAFLD, C57BL/6J mice were given a control diet, high fat and high cholesterol diet (HFD), and HFD plus 2% PS, 1.3% ALA, or 3.3% PS-ALA for 16 weeks. Our results showed that PS-ALA treatment suppressed hepatic steatosis, ameliorated lipid disorder, attenuated inflammatory response, and inhibited oxidative stress. In the molecular level, PS-ALA downregulated high transcriptional and translational levels of endoplasmic reticulum (ER) stress markers (Grp78 and Chop) leading to decreased protein expression of transcription factor and key enzymes involved in de novo lipogenesis (Srebp-1c and Fas) and cholesterol synthesis (Srebp-2 and Hmgcr). In parallel, PS-ALA blocked Nlrp3 activation and reduced release of IL-1ß and IL-18 via inhibiting ER stress-induced sensitization of unfolded protein response sensors (Ire1α and Xbp1s). Finally, PS-ALA improved HFD-induced mitochondrial damage and fatty acid accumulation as exhibited by higher protein and mRNA expression of key genes administering mitochondrial biogenesis (Pgc-1α, Nrf1, and Tfam) and fatty acid ß-oxidation (Pparα and Cpt1a). In conclusion, our study originally demonstrated that PS-ALA rescued ER stress, enhanced mitochondrial biogenesis, and thus ameliorated NAFLD.

Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD).

Application prospective of nanoprobes with MRI and FI dual-modality imaging on breast cancer stem cells in tumor.

Breast cancer (BC) is a serious disease to threat lives of women. Numerous studies have proved that BC originates from cancer stem cells (CSCs). But at present, no one approach can quickly and simply identify breast cancer stem cells (BCSCs) in solid tumor. Nanotechnology is probably able to realize this goal. But in study process, scientists find it seems that nanomaterials with one modality, such as magnetic resonance imaging (MRI) or fluorescence imaging (FI), have their own advantages and drawbacks. They cannot meet practical requirements in clinic. The nanoprobe combined MRI with FI modality is a promising tool to accurately detect desired cells with low amount in tissue. In this work, we briefly describe the MRI and FI development history, analyze advantages and disadvantages of nanomaterials with single modality in cancer cell detection. Then the application development of nanomaterials with dual-modality in cancer field is discussed. Finally, the obstacles and prospective of dual-modal nanoparticles in detection field of BCSCs are also pointed out in order to speed up clinical applications of nanoprobes.