Transcutaneous auricular vagus nerve stimulation for epilepsy.

BACKGROUND: Several studies have suggested that transcutaneous vagus nerve stimulation (tVNS) may be effective for the treatment of epilepsy. However, auricular acupoint therapy (including auricular acupuncture and auricular point-sticking therapy), a method of stimulating the vagus nerve, has been poorly reviewed. This systematic review is the first to categorize auricular acupoint therapy as transcutaneous auricular vagus nerve stimulation (taVNS), aiming to assess the efficacy of taVNS in patients with epilepsy (PWE), and to analyse the results of animal experiments on the antiepileptic effects of taVNS. METHODS: We searched MEDLINE, EMBASE, Web of Science, Scopus, and various Chinese databases from their inception to June 10, 2023 and found nine clinical studies (including a total of 788 PWE) and eight preclinical studies. We performed a meta-analysis and systematic review of these articles to assess the efficacy of taVNS in PWE and the association between taVNS and electroencephalogram (EEG) changes. We also analysed the effects on epileptic behaviour, latency of the first seizure, and seizure frequency in epileptic animals. The PRISMA 2020 checklist provided by the EQUATOR Network was used in this study. RESULTS: taVNS had a higher response rate in PWE than the control treatment (OR = 2.94, 95 % CI = 1.94 - 4.46, P < 0.05). The analysis showed that the taVNS group showed wider EEG changes than the control group (OR = 2.17, 95 % CI 1.03 to 4.58, P < 0.05). The preclinical studies analysis revealed significant differences in epileptic behaviour (SMD = -4.78, 95 % CI -5.86 to -3.71, P < 0.05) and seizure frequency (SMD = -5.06, 95 % CI -5.96 to -4.15, P < 0.05) between the taVNS and control groups. No statistical difference was found in the latency of the first seizure between the two groups (SMD =13.54; 95 % CI 7.76 to 19.33, P < 0.05). CONCLUSION: Based on the available data, PWE may benefit from the use of taVNS. taVNS is an effective procedure for improving epileptic behaviour in animal models.

Formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus globulus subsp. maidenii and their ATP-citrate lyase inhibitory activities.

Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first ß-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis.

Road dust exposure and human corneal damage in a plateau high geological background provincial capital city: Spatial distribution, sources, bioaccessibility, and cytotoxicity of dust heavy metals.

Ocular surface diseases are common in the plateau city, Kunming China, the continued daily exposure to heavy metals in dust may be an important inducement. In this study, the 150 road dust samples from five functional areas in Kunming were collected. The concentrations, distribution, possible sources, and bioaccessibility of heavy metals were analyzed. The adverse effects of dust extracts on human corneal epithelial cells and the underlying mechanisms were also assessed. The concentrations (mg·kg-1) of As (19.1), Cd (2.67), Cr (90.5), Cu (123), Pb (78.4), and Zn (389) in road dust were higher than the soil background, with commercial and residential areas showing the highest pollution. Their bioaccessibility in artificial tears was As (6.59 %) > Cu (5.11 %) > Ni (1.47 %) > Cr (1.17 %) > Mn (0.84 %) > Cd (0.76 %) > Zn (0.50 %) > Pb (0.31 %). The two main sources of heavy metals included tire and mechanical abrasion (24.5 %) and traffic exhaust (21.6 %). All dust extracts induced cytotoxicity, evidenced by stronger inhibition of cell viability, higher production of ROS, and altered mRNA expression of antioxidant enzymes and cell cycle-related genes, with commercial- areas-2 (CA2)-dust extract showing the greatest oxidative damage and cell cycle arrest. Our data may provide new evidence that dust exposure in high geological background cities could trigger human cornea damage.

Shengmai injection inhibits palmitic acid-induced myocardial cell inflammatory death via regulating NLRP3 inflammasome activation.

Objective: To determine the protective effect of Shengmai injection (SMI) on myocardial injury in diabetic rats and its mechanism based on NLRP3/Caspase1 signaling pathway. Materials and methods: Rat H9c2 cardiomyocytes were cultured in vitro, and the cell survival rate of different concentrations of palmitate acid (PA) and different concentrations of SMI were detected by CCK-8. The myocardial injury cell model was induced with PA, treated with SMI, and combined with NLRP3 specific inhibitor (MCC950) to interfere with the high-fat-induced rat H9c2 myocardial cell injury model. The cell changes were observed by Hoechst/PI staining and the expression levels of MDA, SOD, and ROS in each group were detected. The protein and gene changes of the NLRP3/Caspase-1 signaling pathway were detected by Western blot and RT-qPCR, respectively. Results: 200 µmol/L of PA were selected to induce the myocardial injury cell model and 25 µL/mL of SMI was selected for intervention concentration. SMI could significantly reduce MDA expression, increase SOD level, and decrease ROS production. SMI could decrease the gene expression levels of NLRP3, ASC, Caspase-1, and GSDMD, and the protein expressions of NLRP3, ASC, Cleaved Caspase-1, GSDMD, and GSDMD-N. Conclusion: SMI can inhibit the high-fat-induced activation of the NLRP3/Caspase-1 signaling pathway, intervene in cardiomyocyte pyroptosis, and prevent diabetic cardiomyopathy.

A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study.

A new class of potent liver injury protective compounds, phychetins A-D (1-4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2-4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1-4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2-4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1ß. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway.

CONTEXT: Punicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear. OBJECTIVE: These studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI. MATERIALS AND METHODS: Molecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) groups for 4 weeks. Thoracotomy with perforation but no ligature was performed on rats in control group. The protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and GSDMD-N, the mRNA expression of NLRP3, caspase-1, GSDMD, interleukin-1ß (IL-1ß) and IL-18 were evaluated. RESULTS: Punicalagin had binding activities with NLRP3 (Vina score, -5.8), caspase-1 (Vina score, -6.7), and GSDMD (Vina score, -6.7). Punicalagin could improve cardiac function, alleviate cardiac pathological changes, minimize the excessive accumulation of collagen in the left ventricular myocardium (p < 0.01), and inhibit cardiomyocyte apoptosis (p < 0.01). Furthermore, punicalagin could inhibit the overexpression of NLRP3, caspase-1, and GSDMD via immunohistochemistry (p < 0.01). Punicalagin inhibited the protein levels of NLRP3, caspase-1, ASC, GSDMD, and GSDMD-N (p < 0.05, p < 0.01). Punicalagin reduced the mRNA expression of NLRP3, caspase-1, GSDMD, IL-1ß and IL-18 (p < 0.05, p < 0.01). CONCLUSIONS: Punicalagin may provide a useful treatment for the future myocardial protection.

Enantiomeric pairs of macrocyclic acylphloroglucinols from Syzygium szemaoense.

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.

A review of the current research on in vivo and in vitro detection for alpha-synuclein: a biomarker of Parkinson's disease.

Parkinson's disease is a health-threatening neurodegenerative disease of the elderly with clinical manifestations of motor and non-motor deficits such as tremor palsy and loss of smell. Alpha-synuclein (α-Syn) is the pathological basis of PD, it can abnormally aggregate into insoluble forms such as oligomers, fibrils, and plaques, causing degeneration of nigrostriatal dopaminergic neurons in the substantia nigra in the patient's brain and the formation of Lewy bodies (LBs) and Lewy neuritis (LN) inclusions. As a result, achieving α-Syn aggregate detection in the early stages of PD can effectively stop or delay the progression of the disease. In this paper, we provide a brief overview and analysis of the molecular structures and α-Syn in vivo and in vitro detection methods, such as mass spectrometry, antigen-antibody recognition, electrochemical sensors, and imaging techniques, intending to provide more technological support for detecting α-Syn early in the disease and intervening in the progression of Parkinson's disease.

Acylphloroglucinol-monoterpene meroterpenoids from Eucalyptus tereticornis and their inhibitory activity against ATP citrate lyase.

Five undescribed enantiomeric pairs of acylphloroglucinol-monoterpene meroterpenoids ((+)-/(-)-eucateretins A-E) resolved by chiral-phase HPLC were obtained from the leaves of Eucalyptus tereticornis Smith, along with nine known analogues. Their structures were elucidated by spectroscopic methods and ECD calculations. This is the first report of meroterpenoid enantiomers from this plant. Some of the isolates, (-)-eucateretin A, (+)-/(-)-eucateretins E, 7'α-eucalrobusone X, eucalrobusone X, and robustadial B, exhibited inhibitory effects on ATP citrate lyase, and 7'α-eucalrobusone X significantly suppressed the hepatocyte lipogenesis.

The Protective Effect of Sheng Mai Yin on Diabetic Cardiomyopathy via NLRP3/Caspase-1 Pathway.

Sheng Mai Yin (SMY) has therapeutic effects on myocardial infarction (MI), heart failure (HF), diabetic cardiomyopathy (DCM), and myocarditis. To study whether SMY can relieve pyroptosis and play a protective role in diabetic cardiomyopathy, a molecular docking technique was used to predict the possible mechanism of SMY against DCM. Then, a DCM rat model was induced by intraperitoneal injection of streptozotocin (STZ), divided into 5 groups: the DM group (model), SMY-L group (2.7 mL/kg SMY), SMY-M group (5.4 mL/kg SMY), SMY-H group (10.8 mL/kg SMY), and Met group (120 mg/kg metformin). Rats in the CTL group (control) and DM group were given normal saline. After 8 weeks, the levels of blood glucose, lipids, and myocardial enzymes were detected according to the kit instructions. Cardiac function was detected by echocardiography. HE and Masson were used to observing the pathological changes, collagen deposition, and collagen volume fraction (CVF). The apoptosis rate of cardiomyocytes was determined by Tunel. The IL-1ß level was determined by ELISA and RT-PCR. The expressions of NLRP3, caspase-1, and GSDMD were measured using RT-PCR and Western blotting. The docking results suggested that SMY may act on NLRP3 and its downstream signal pathway. The in vivo results showed that SMY could reduce blood glucose and lipid levels, improve heart function, improve histopathological changes and myocardial enzymes, and alleviate cardiomyocyte apoptosis and myocardial fibrosis. SMY inhibited the mRNA and protein expressions of NLRP3, ASC, Caspase-1, and GSDMD and IL-1ß production. SMY can reduce DCM by regulating the NLRP3/caspase-1 signaling pathway, providing a new research direction for the treatment of DCM.

Organophosphorus Flame Retardant TCPP Induces Cellular Senescence in Normal Human Skin Keratinocytes: Implication for Skin Aging.

Tris (1-chloro-2-propyl) phosphate (TCPP) is one of the most frequently detected organophosphorus flames in the environment. Continuous daily exposure to TCPP may harm human skin. However, little is known about the adverse effects of TCPP on human skin. In this study, we first evaluated the detrimental effects and tried to uncover the underlying mechanisms of TCPP on human skin keratinocytes (HaCaT) after 24 h exposure. We found that TCPP caused a concentration-dependent decrease in HaCaT cell viability after exposure to 1.56-400 µg/mL for 24 h, with an IC50 of 275 µg/mL. TCPP also promoted the generation of intracellular reactive oxygen species (ROS) and triggered DNA damage, evidenced by an increase of phosphorylated histone H2A.X (γH2A.X) in the nucleus. Furthermore, the cell cycle was arrested at the G1 phase at 100 µg/mL by upregulation of the mRNA expression of p53 and p21 and downregulation of cyclin D1 and CDK4 expression. Additionally, both the senescence-associated-ß-galactosidase activity and related proinflammatory cytokine IL-1ß and IL-6 were elevated, indicating that TCPP exposure caused cellular senescence may be through the p53-dependent DNA damage signal pathway in HaCaT cells. Taken together, our data suggest that flame-retardant exposure may be a key precipitating factor for human skin aging.

Mechanisms of Cd-Induced Cytotoxicity in Normal Human Skin Keratinocytes: Implication for Human Health.

Cadmium (Cd) is one of the toxic heavy metals found widely in the environment. Skin is an important target organ of Cd exposure. However, the adverse effects of Cd on human skin are still not well known. In this study, normal human skin keratinocytes (HaCaT cells) were studied for changes in cell viability, morphology, DNA damage, cycle, apoptosis, and the expression of endoplasmic reticulum (ER) stress-related genes (XBP-1, BiP, ATF-4, and CHOP) after exposure to Cd for 24 h. We found that Cd decreased cell viability in a concentration-dependent manner, with a median lethal concentration (LC50) of 11 µM. DNA damage induction was evidenced by upregulation of the level of γ-H2AX. Furthermore, Cd induced G0/G1 phase cell cycle arrest and apoptosis in a dose-dependent manner and upregulated the mRNA levels of ER stress biomarker genes (XBP-1, BiP, ATF4, and CHOP). Taken together, our results showed that Cd induced cytotoxicity and DNA damage in HaCaT cells, eventually resulting in cell cycle arrest in the G0/G1 phase and apoptosis. In addition, ER stress may be involved in Cd-induced HaCaT apoptosis. Our data imply the importance of reducing Cd pollution in the environment to reduce its adverse impacts on human skin.

Physical activity alleviates negative effects of bedroom light pollution on blood pressure and hypertension in Chinese young adults.

Excessive exposure to light at night (LAN) has become a serious public health concern. However, little is known about the impact of indoor LAN exposure on blood pressure, particularly among young adults. We aimed to investigate the effects of bedroom individual-level LAN exposure in real-world environment on blood pressure and hypertension among vulnerable young adults, and to evaluate the possible buffering effect of physical activity. In this cross-sectional study, a total of 400 healthy young adults aged 16-22 years were included. Bedroom LAN exposure was recorded at 1-min intervals for two consecutive nights using a TES-1339 R illuminance meter. Blood pressure was measured three times (8-11 a.m. in the physical examination day) in the seated position using an Omron HEM-7121 digital sphygmomanometer. A wrist-worn triaxial accelerometer (ActiGraph GT3X-BT) was used to assess physical activity for seven consecutive days. Each 1 lx increase of bedroom LAN intensity was associated with 0.55 mmHg-increase in SBP (95% CI: 0.15, 0.95), 0.30 mmHg-increase in DBP (95% CI: 0.06, 0.54), and 0.38 mmHg-increase in MAP (95% CI: 0.12, 0.65). Higher levels of LAN exposure were associated with increased risk of hypertension (LAN ≥ 3lx vs. LAN < 3lx: OR = 3.30, 95%CI = 1.19-9.19; LAN ≥ 5lx vs. LAN < 5lx: OR = 3.87, 95%CI = 1.37-10.98). However, these detrimental effects of bedroom LAN exposure on blood pressure and hypertension were not observed among young adults with high MVPA (≥2 h/day) level. MVPA can alleviate negative effects of bedroom LAN exposure on blood pressure and hypertension. Maintaining bedroom settings darkness at night may be an important strategy for reducing the risk of hypertension. Furthermore, for individuals living with high levels of indoor LAN exposure, regular physical activity may be a good option for preventing cardiovascular disease and hypertension.

Dexmedetomidine prevents hemorrhagic brain injury by reducing damage induced by ferroptosis in mice.

Intracerebral hemorrhage (ICH) is a devastating condition with significant morbidity and mortality for which few effective treatments are clinically available. After ICH, iron overload within the perihaematomal region can induce lethal reactive oxygen species (ROS) production and lipid peroxidation, which contribute to secondary brain injury. An iron-dependent form of non-apoptotic cell death known as ferroptosis was recently identified. Ferroptosis plays an important role in ICH pathology. It is characterized by an accumulation of iron-induced lipid ROS, which leads to intracellular oxidative stress. Dexmedetomidine (DEX), an α2-adrenergic agonist, is widely used for anesthesia, pain control, and intensive care unit sedation. DEX has numerous beneficial activities, including anti-inflammatory, anti-oxidative, and anti-cell death activities. Here, we established a mouse model of ICH using collagenase VII and evaluated the effect of DEX in preventing ICH-induced brain injury. Our study showed that administering DEX reduced the damage induced by ferroptosis after ICH by regulating iron metabolism, amino acid metabolism and lipid peroxidation processes.

Is farmland financial innovation narrowing the urban-rural income gap? A cross-regional study of China.

Over the past four decades, China's economy has experienced tremendous economic growth but also a widening urban-rural income gap. Given the dilemma of the urban-rural income gap in China explained by neoclassical equilibrium theory, this paper attempts to provide a new theoretical explanation for the large-income gap between urban and rural areas in China. We select data from 30 provinces(cities) in China over the period from 2006 to 2017 as a sample to investigate whether and how the degree of farmland financial innovation narrows the urban-rural income gap. The results show that the coefficient for farmland financial innovation is significantly negative at the 1% level, signifying that financial innovation can narrow the urban-rural income gap in China. The mediation effect test provides evidence that farmland financial innovation narrows the urban-rural income gap by promoting the permanent migration of the labor force and upgrading the industrial structure. Our results indicate that the government should promote various forms of farmland financial innovation, establish rural property rights transaction system and free farmers from deep farmer-land attachment to realize permanent labor migration.

Kaempferol-3-O-rutinoside exerts cardioprotective effects through NF-κB/NLRP3/Caspase-1 pathway in ventricular remodeling after acute myocardial infarction.

Ventricular remodeling (VR) after acute myocardial infarction (AMI) is the main pathogenesis of chronic heart failure (CHF). Kaempferol-3-O-rutinoside (KR) is the flavonoid glycoside with the highest content in Lu'an GuaPian tea, which has good pharmacological activities. However, the mechanism of KR against VR after AMI remains unclear. Molecular docking was used to predict the targets of KR on the NLRP3/Caspase-1 signaling pathway. Histological changes in the myocardium were visualized using HE staining, Masson staining. Cardiomyocyte apoptosis was detected using TUNEL. Immunohistochemistry was used to examine NLRP3, Caspase-1 p20, and GSDMD. IL-1ß level in serum was detected using ELISA. Finally, the expressions of NF-κB p65, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1ß were measured using RT-PCR and Western blotting. Our results showed that KR had a good binding activity with NLRP3, Caspase-1, and GSDMD, significantly improved cardiac function, alleviated cardiac pathological changes, reduced the excessive deposition of myocardial interstitial collagen, and inhibited cardiomyocyte apoptosis in AMI rats. Furthermore, KR could decrease the IL-1ß level and inhibit the expressions of NF-κB p65, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1ß. Our study suggests that KR can prevent and treat VR after AMI, and the protective effect is related to its regulatory NF-κB/NLRP3/Caspase-1 signaling pathway. PRACTICAL APPLICATIONS: Kaempferol-3-O-rutinoside is present in Carthamus tinctorius L., Nymphaea candida, Afgekia mahidoliae and green tea, which has good pharmacological activities against liver injury, cerebral ischemia/reperfusion injury, dementia, hyperglycemia, and myocardial infarction. Our previous study found that kaempferol-3-O-rutinoside had an obvious anti-inflammatory effect, and could significantly improve the cell survival rate of H9c2 myocardium inflammatory injury induced by LPS. In this study, kaempferol-3-O-rutinoside significantly improved cardiac function, alleviated cardiac pathological changes, reduced the excessive deposition of myocardial interstitial collagen, and inhibited cardiomyocyte apoptosis in AMI rats. Furthermore, kaempferol-3-O-rutinoside could decrease the IL-1ß level and inhibit the expressions of NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD and IL-1ß, suggesting that kaempferol-3-O-rutinoside could regulate NF-κB/NLRP3/Caspase-1 signaling pathway.

Quinoline alkaloids with anti-inflammatory activity from Zanthoxylum avicennae.

Zanthoxylum avicennae fruits were traditionally used to treat many inflammatory-related diseases, such as icterohepatitis, nephritis and colitis, which inspired us to explore the active chemicals and pharmacological activity. As a result, ten quinoline alkaloids, including six new ones, avicenines A-F (1-6), were isolated and structurally characterized by solid data. Compounds 1, 7 and 8 were identified as three pairs of enantiomers by chiral HPLC separation, of which 1 was an unusual 6/6/5/5-fused quinoline alkaloid bearing a unique cis-hexahydrofuro[3,2-b]furan moiety. The putative biosynthetic pathway for enantiomeric compounds was also proposed. In addition, compound 6 significantly suppressed the gene expression and secretion of pro-inflammatory cytokines IL-1ß and IL-6 in macrophages.

Dexmedetomidine Alleviates Intracerebral Hemorrhage-Induced Anxiety-Like Behaviors in Mice Through the Inhibition of TRPV4 Opening.

Post-stroke anxiety severely affects recovery in patients with intracerebral hemorrhage (ICH). Dexmedetomidine (Dex), a highly selective alpha 2 adrenal receptor (α2-AR) agonist, was recently found to exert an excellent protective effect against mental disorders including anxiety. The transient receptor potential vanilloid 4 (TRPV4) channel is involved in a series of diseases such as asthma, cancer, anxiety, and cardiac hypertrophy. This study examines whether Dex improved ICH-induced anxiety via the inhibition of TRPV4 channel opening. A rodent model of moderate ICH in the basal ganglia was established using autologous blood injection (20 µl). Mice were treated with Dex (25 µg/kg, intraperitoneal injection) every day for 3 days post-ICH. GSK1016790A (1 µmol/2 µl), an agonist of TRPV4, was administered via the left lateral ventricle. Thirty days post-ICH, post-stroke anxiety was evaluated by elevated plus-maze and open-field tests. Following behavioral tests, superoxide dismutase (SOD), malondialdehyde (MDA), astrocytic activation, and A1-and A2-type astrocytes were determined. Primary astrocytes were exposed to hemin to simulate ICH in vitro. Compared with sham-treated mice, Dex administration ameliorates ICH-induced decreases of distance and time in the open-arm, reduces distance and time in the central zone, increases astrocytic activation and A1-type astrocytes, elevates MDA content, downregulates total SOD contents, and decreases A2-type astrocytes. However, GSK1016790A partially reversed the neuroprotective effects of Dex. In addition, Dex significantly inhibited hemin-induced astrocytic activation in vitro. Dex improves ICH-induced anxiety-like behaviors in mice, and the mechanism might be associated with the inhibition of TRPV4-channel opening.

Dermal bioaccessibility and cytotoxicity of heavy metals in urban soils from a typical plateau city: Implication for human health.

The dermal exposure of heavy metals in contaminated urban soils poses huge environmental health risks globally. However, their dermal bioaccessibility and adverse effects on human skin cells were not fully understood. In this study, we measured the total and dermal bioaccessibility of Cr, As, Cd, Pb, and Cu in four selected urban soil samples from Kunming, Yunnan, China, and evaluated the cellular responses of these bioaccessible extracts on human keratinocytes (HaCaT). Among all the metals, only As in Soil-3 (S3) exceeded Chinese risk screening and Yunnan background values at 38.2 mg/kg. The average concentrations of Cr, As, Cd, Pb, and Cu in all soil samples were 47.79, 15.50, 3.11, 104.27, and 180.29 mg/kg respectively. Although relatively high concentrations of heavy metals were detected in soil samples, the highest dermal bioaccessibility of Cd was 3.57% with others' being lower than 1%. The bioaccessible dermal-absorbed doses (DADs) of Cr, As, Cd, Pb, and Cu from soils reflected acceptable health risks since all DADs were below the corresponding derived dermal reference values. However, the toxic data showed the extracts of S3 and S4 presented certain cytotoxicity in HaCaT cells, indicating the existing models based on dermal bioaccessibility and DADs may be not accurate enough to assess their human health risk. Taken together, the human health risk assessment should be modified by taking their skin cytotoxicity into account.

The crucial role of thioredoxin interacting protein in the liver insulin resistance induced by di (2-ethylhexyl) phthalates.

The widespread usage of plastic products in human life has led to extensive exposure to plasticizers and resulted in serious health problems for humans, which has become a focus of toxicology research in the world. We aimed to explore the potential mechanism of liver insulin resistance induced by di(2-ethylhexyl) phthalate (DEHP) and working on a novel treatment to alleviate insulin resistance caused by excessive exposure to DEHP. For this purpose, in vivo and in vitro experiments were conducted, and the pivotal factors in the insulin signaling pathway were analyzed. In vivo study showed DEHP could lead to liver injury and insulin resistance. DEHP could break the balance of oxidative stress and cause accumulation of inflammatory factors. Genomics and proteomics experiment results revealed that DEHP could inhibit the mRNA and protein expression of insulin receptor, insulin receptor substrate, PI3K/Akt/mTOR, and glucose transporter 4. Nevertheless, the liver insulin resistance induced by DEHP could be reversed by Verapamil (thioredoxin interacting protein (TXNIP) inhibitor). Thus, we confirmed that DEHP caused insulin resistance by affecting the TXNIP in liver, further damaging the conduction of insulin signaling pathway. Therefore, adding Verapamil to the treatment of patients with insulin resistance due to plasticizers might be more effective.