Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Non-CO2 greenhouse gas separation using advanced porous materials.

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

Melatonin inhibits atrazine-induced mitochondrial impairment in cerebellum of mice: Modulation of cGAS-STING-NLRP3 axis-dependent cell pyroptosis.

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.

The value of transthoracic echocardiography and chest X-ray in locating the tip of central venous catheter in dialysis patients: a comparative study with computed tomography imaging.

To determine the tip position of the central venous catheter (CVC) in patients with dialysis, the guidelines recommend that it be determined using chest radiography (CXR) after catheterization, without fluoroscopy. However, some researchers have proposed that transthoracic echocardiography (TTE) can replace CXR, but this has not been widely adopted. This study aimed to determine which of the two aforementioned methods is more suitable for locating the tip position of the CVC. This prospective study included 160 patients who underwent hemodialysis at our hospital from March 2021 to December 2022. After inserting the CVC through the internal jugular vein, we used transthoracic echocardiography and CXR to determine the tip of the CVC and compared the results with those of computed tomography (CT). In the comparison between TTE and CXR for locating the CVC tip, we obtained three main findings. (1) TTE was associated with fewer misdiagnosed cases than CXR. (2) TTE provided higher sensitivity (similar sensitivity in position 2), specificity, positive/negative predictive values, and accuracy than CXR. (3) When comparing the receiver operating characteristic curves of TTE and CXR, the area under the curve (95% confidence interval) for the former was larger. Additionally, we made anatomical discoveries: the "hyperechoic triangle" recognized by TTE was equivalent to the entrance of the superior vena cava into the right atrium shown by transesophageal transthoracic echocardiography. TTE is more suitable than CXR as the first examination for CVC tip localization, as it improves diagnostic accuracy and reduces X-ray radiation damage.

Exploring the structure of the shot effectiveness model for elite table tennis players.

BACKGROUND: Currently, technical and tactical analysis has become an indispensable task for sport in many countries. Many studies analysed players' specific technical and tactical factors, but it is rare to quantitatively analyse the importance of table tennis players' shot effectiveness. This is the first study to propose the new concept of "shot effectiveness model", and the purpose of this study is to explore the structure of the shot effectiveness model for elite table tennis, including the importance degree of shot effectiveness, and the relationship between them. METHODS: 258 matches were selected between the top 50 players in the world from 2019 to 2021 as samples. Multiple regression analysis was used to obtain the standard regression coefficients and game simulation, and the total decision coefficient (TDC) was used to evaluate the importance degrees of shot effectiveness (SE) on match results. RESULTS: (1) There was little difference in the importance degree of each shot effectiveness between men and women players. (2) The importance degree of the first and third shots (SE1), the second and fourth shots (SE2), the fifth and after shots (SE3), and the sixth and after shots (SE4) for both men and women players account for approximately 25%, 35%, 22%, and 16% respectively. (3) There was little difference in the importance degree of each shot effectiveness between Chinese women players and women players from other countries and regions with the same importance order of SE2 > SE1 > SE3 > SE4. However, the structure of the shot effectiveness model for men players was quite different from that for women players. (4) There is a compensation effect between shot effectiveness of table tennis players, and the total evaluation score of 12 and 13 is the dividing line for success or failure in both men and women matches. CONCLUSIONS: TDC could well reflect the important degrees of each shot effectiveness in various ways on winning probability in table tennis matches. And this study compared the importance of several types of players' performance on the probability of winning a match. In addition, we found that there is a compensation effect between shot effectiveness of table tennis players, and the magnitude of this effect will vary according to the type and level of shot effectiveness.

Lycopene Prevents Phthalate-Induced Cognitive Impairment via Modulating Ferroptosis.

Di-(2-ethylhexyl) phthalate (DEHP) is frequently used as a plasticizer in industrial and agricultural products. DEHP can cause severe neurotoxicity, such as impaired learning and memory function. Lycopene (LYC) as a carotenoid exerts excellent antioxidant capacity and therapeutic effects in neurodegenerative diseases. However, whether LYC can prevent the cognitive impairment induced by DEHP and the specific mechanisms are unclear. In the present study, the behavioral test results suggested that LYC alleviated the learning and memory impairment induced by DEHP. The histopathological data revealed that LYC attenuated DEHP-induced disordered arrangement of the neurons in the CA1 and CA3 regions of the hippocampus tissue. Moreover, LYC inhibited the occurrence of DEHP-induced ferroptosis via regulating iron metabolism, inhibiting lipid peroxidation, and activating the cysteine transporter and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (NrF2/HO-1) signaling pathway. Overall, the study contributes novel perspectives into the potential mechanisms of LYC preventing phthalate-induced cognitive impairment in the hippocampus.

Lycopene prevents Di-(2-ethylhexyl) phthalate-induced mitophagy and oxidative stress in mice heart via modulating mitochondrial homeostasis.

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is easily found in the environment. Excessive daily exposure of it may lead to an increased risk of cardiovascular disease (CVD). Lycopene (LYC), as a natural carotenoid, has been shown to have the potential to prevent CVD. However, the mechanism of LYC on cardiotoxicity caused by DEHP exposure is unknown. The research was aimed to investigate the chemoprotection of LYC on the cardiotoxicity caused by DEHP exposure. Mice were treated with DEHP (500 mg/kg or 1,000 mg/kg) and/or LYC (5 mg/kg) for 28 d by intragastric administration, and the heart was subjected to histopathology and biochemistry analysis. The results indicated that DEHP caused cardiac histological alterations and enhanced the activity of cardiac injury indicators, and interfered with mitochondrial function and activating mitophagy. Notably, LYC supplementation could inhibit DEHP-induced oxidative stress. The mitochondrial dysfunction and emotional disorder caused by DEHP exposure were significantly improved through the protective effect of LYC. We concluded that LYC enhances mitochondrial function by regulating mitochondrial biogenesis and dynamics to antagonize DEHP-induced cardiac mitophagy and oxidative stress.

Lycopene ameliorates DEHP exposure-induced renal pyroptosis through the Nrf2/Keap-1/NLRP3/Caspase-1 axis.

Di (2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in plastic products, and due to its unique chemical composition, it frequently dissolves and enters the environment. Lycopene as a natural carotenoid has been shown to have powerful antioxidant capacity and strong kidney protection. This study aimed to investigate the role of the interplay between oxidative stress and the classical pyroptosis pathway in LYC alleviating DEHP-induced renal injury. ICR mice were given DEHP (500 mg/kg/d or 1000 mg/kg/d) and/or LYC (5 mg/kg/d) for 28 days to explore the underlying mechanisms of this hypothesis. Our results indicated that DEHP caused the shedding of renal tubular epithelial cells, increased the content of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the tissue, the decrease of antioxidant activity markers and the increase of oxidative stress indexes. It is gratifying that LYC alleviates DEHP-induced renal injury. The expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) and its downstream target genes is improved in DEHP induced renal injury through LYC mediated protection. Meanwhile, LYC supplementation can inhibit DEHP-induced Caspase-1/NLRP3-dependent pyroptosis and inflammatory responses. Taken together, DEHP administration resulted in nephrotoxicity, but these changes ameliorated by LYC may through crosstalk between the Nrf2/Keap-1/NLRP3/Caspase-1 pathway. Our study provides new evidence that LYC protects against kidney injury caused by DEHP.

Phthalate induces mitochondrial injury in cerebellum through Sirt1-PGC-1α and PINK1/Parkin-mediated signal pathways.

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental toxicant that is widely used in the whole world as a plasticizer that can enhance plastic properties. A number of reserarches have demonstrated that DEHP could cause varying degrees of damage to the normal function of nerve. The research aimed to investigate the mechanism of DEHP-induced cerebellar toxicity. In present study, we set DEHP-caused cerebellar injury models of quail and implied that DEHP induced cerebellar dysplasia by abnormity of Purkinje cell and reduction of cerebellar granule cell. Furthermore, the mitochondrial damage was confirmed by the swelling, cristae reduction, membrane rupture of mitochondria or even the occurrence of autophagic vacuole. To clarified DEHP-induced mitochondrial damage in cerebellum, we examined the relevant genes of mitochondrial biogenesis, mitochondrial dynamics, oxidative damage, the pathways related to Nrf2 and PINK1/Parkin in cerebellum. Based on data, it appeared that DEHP treatment had a damaging effect on the cerebellum and led to mitophagy as well as oxidative stress. In conclusion, the research indicated that DEHP-actuated mitochondrial injury has a directly relationship with mitophagy. DEHP-actuated reduced mitochondrial biogenesis and dysregulation of mitochondrial dynamics. The increase of oxidative stress damaged mitochondria, and the redundant ROS in damaged mitochondria that gave rise to cerebellar harm.

Xenobiotic-sensing nuclear receptors as targets for phthalates-induced lung injury and antagonism of lycopene.

Phthalates are extensively used in the production of plastics products and have been verified to induce lung injury. Lycopene (LYC) has proved an effective preventive and can be utilized to prevent phthalates-induced toxicity. However, the role of phthalate in pathogenesis of lung injury remain poorly researched, and little work has been devoted whether LYC could alleviate phthalate-induced lung toxicity via modulating nuclear xenobiotic receptors (NXRs) response. Here, di (2-ethylhexyl) phthalate (DEHP) is used as the representative of phthalates for further studies on toxicity of phthalates and the antagonistic role of LYC in phthalates-induced lung injury. We found that DEHP exposure caused alveoli destruction and alveolar epithelial cells type II damage. Mechanistically, DEHP exposure increased nuclear accumulation of aryl hydrocarbon receptor (AHR) and its downstream genes level, including cytochrome P450-dependent monooxygenase (CYP) 1A1 and CYP1B1. Constitutive androstane receptor (CAR) and their downstream gene level, including CYP2E1 are also increased after phthalates exposure. Significantly, LYC supplementation relieves lung injury from DEHP exposure by inhibiting the activation of NXRs. We confirm that NXRs plays a key role in phthalates-induced lung injury. Our study showed that LYC may have a positive role in alleviating the toxicity effects of phthalates, which provides an effective strategy for revising phthalates-induced injury.

Lycopene Attenuates Di(2-ethylhexyl) Phthalate-Induced Mitochondrial Damage and Inflammation in Kidney via cGAS-STING Signaling.

Di(2-ethylhexyl) phthalate (DEHP) is a highly harmful and persistent environmental pollutant. Due to its unique chemical composition, it frequently dissolves and enters the environment to endanger human and animal health. Lycopene is a natural bioactive component that can potentially reduce the risk of environmental factor-induced chronic diseases. The present study sought to explore the role and underlying mechanism of lycopene (LYC) on DEHP-induced renal inflammatory response and apoptosis. In this study, mice were orally treated with LYC (5 mg/kg BW/day) and/or DEHP (500 or 1000 mg/kg BW/day) for 28 days. Our results indicated that LYC prevented DEHP-induced histopathological alterations and ultrastructural injuries, including decreased mitochondrial membrane potential (ΔΨm), PINK1/Parkin pathway-mediated mitophagy, and mitochondrial energetic deficit. When damaged mitochondria release mitochondrial DNA (mtDNA) into cytosol, LYC can alleviate inflammation and apoptosis caused by DEHP exposure by activating the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) signal pathway. Collectively, our data demonstrate that LYC can reduce mitophagy caused by DEHP exposure by activating the PINK1/Parkin pathway and then reduce renal inflammation and apoptosis through the cGAS-STING pathway.

LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis.

Introduction: Chronic endometritis is a common disease in women of childbearing age and can cause pelvic inflammatory disease. The cGAS-STING pathway plays an important role in many inflammatory diseases. Purpose: The aim of this study was to investigate the relationship between the cGAS-STING pathway and endometritis. Methods: We collected endometrium samples from patients with endometritis to detect changes in the cGAS-STING pathway. In vitro, human endometrial stromal cells (HESC) were stimulated with lipopolysaccharide (LPS), and a mouse STING gene-knockout model was established by CRISPR/cas9 for STING to further explore the mechanism underlying its effects in endometritis. We used Western blotting (WB) and immunohistochemical staining to detect the variations in protein levels and real-time PCR to study the variations in gene expression. Results: We observed the activation of the cGAS-STING pathway and an increase in the expression of cytokine-encoding genes, including IL-8, IL-6, IL-1ß, and IFN-ß1, in endometrial tissues of patients with endometritis. Stimulation of HESCs using LPS demonstrated increase in the expression of proteins involved the cGAS-STING pathway and the gene expression of inflammatory cytokines. STING-knockdown experiments demonstrated a decrease in the gene expression levels of inflammatory cytokines. Moreover, we also identified the translocation of IRF3 and STING after LPS stimulation. Regarding mitochondrial function, LPS led to an increase in reactive oxygen species levels and a reduction in mitochondrial membrane potential. However, we observed that the mitochondrial DNA (mtDNA) leaked into the cytoplasm, upregulating the levels of proteins involved in the cGAS-STING pathway upon LPS stimulation. Furthermore, our results showed that LPS induced hyperemia, inflammatory factor production, and expression of Pho-TBK1 in wild-type mice compared with the levels in control mice, and STING gene-knockdown alleviated these effects. Conclusion: LPS induces mitochondrial dysfunction in endometrial stromal cells, resulting in mtDNA leakage and promoting endometritis by stimulating the cGAS-STING pathway.

Lycopene alleviates di(2-ethylhexyl) phthalate-induced splenic injury by activating P62-Keap1-NRF2 signaling.

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage.

Role of Toll-like Receptor/MyD88 Signaling in Lycopene Alleviated Di-2-ethylhexyl Phthalate (DEHP)-Induced Inflammatory Response.

Lycopene (Lyc) has anti-inflammatory and antioxidant biological functions. Di-2-ethylhexyl phthalate (DEHP) is an extremely harmful and persistent environmental pollutant and is a threat to animal health. The toll-like receptor (TLR)/MyD88 pathway is an important pathway in the inflammatory response. To illustrate the potential antagonistic action of Lyc against DEHP by the TLR/MyD88 pathway, 140 ICR mice were randomly assigned groups and continuously gavaged with corn oil, distilled water, different DEHP concentrations (500 or 1000 mg/kg BW/day), and/or Lyc (5 mg/kg BW/day) for 28 days. The data show that Lyc effectively attenuates the DEHP-induced activation of the TLR/MyD88 pathway, the upregulation of JNK expression, the content of IL-6 and TNF-α, and the downregulation of the IL-10 content, which eventually inhibit the inflammatory response and mitochondrial injuries. These findings underline the TLR/MyD88 pathway as a potential therapeutic target in DEHP and Lyc as a new therapeutic method to inhibit DEHP toxicity.

Echocardiography in the diagnosis of Shone's complex and analysis of the causes for missed diagnosis and misdiagnosis.

BACKGROUND: Shone's complex is a rare syndrome characterized by congenital left heart defects that can differ among the patients. AIM: To use echocardiography in the diagnosis of Shone's complex and analyze the causes of missed diagnosis and misdiagnosis. METHODS: This was a retrospective study of patients who underwent echocardiography and repair surgery from February 14, 2008, to November 22, 2019. The patients were followed once a year at the outpatient clinic after surgery. RESULTS: Sixty-six patients were included. The patients were 2.7 (0.8-5.6) years of age, and 54.5% were male. Ten (15.2%) had a history of heart surgery. The most common heart defect was the Annulo-Leaflet mitral ring (ALMR) (50/66, 75.8%), followed by coarctation of the aorta (CoA) (43/66, 65.2%). The patients had a variety of combinations of defects. Only two (3.0%) patients had all four defects. None of the patients had a family history of congenital heart disease. The preoperative echocardiographic findings were examined against the intraoperative findings. Echocardiography missed an ALMR in 31 patients (47.0%), a parachute mitral valve (PMV) in one patient (1.5%), subaortic stenosis in one patient (1.5%), and CoA in two patients (3.0%). CONCLUSION: Echocardiography is an effective method to diagnose the Shone's complex. Due to this disease's complexity and interindividual variability, Improving the understanding of the disease can reduce misdiagnosis and missed diagnosis.

Role of mitochondria-endoplasmic reticulum coupling in lycopene preventing DEHP-induced hepatotoxicity.

Di (2-ethylhexyl) phthalate (DEHP) is a hazardous compound used as a plasticizer in plastic products. As a natural carotenoid, lycopene (LYC) is considered an effective protective agent against various types of organ damage. The present study aimed to investigate the role of mitochondria-endoplasmic reticulum (ER) coupling in LYC preventing DEHP-induced hepatotoxicity. The mice were treated with LYC (5 mg kg-1) and/or DEHP (500 or 1000 mg kg-1). In the present study, LYC prevented DEHP-induced histopathological changes including fibrosis and glycogen storage in the liver. Additionally, LYC alleviated DEHP-induced ultrastructural injury of mitochondria and ER. LYC had the underlying preventability against DEHP-induced mitochondrial dynamics imbalance including an increase in fission and a decrease in fusion. Furthermore, DEHP induced mitochondria-associated endoplasmic reticulum membrane (MAM) disorder-induced ER stress through the ER unfolded protein response (UPRER), but LYC alleviated these alterations. Therefore, LYC prevented DEHP-induced hepatic mitochondrial dynamics and MAM disorder, leading to ER stress. The present study provides novel evidence of mitochondria-ER coupling as a target for LYC that prevents DEHP-induced hepatotoxicity.

Lycopene Preventing DEHP-Induced Renal Cell Damage Is Targeted by Aryl Hydrocarbon Receptor.

Di (2-ethylhexyl) phthalate (DEHP) is an environmentally persistent and bioaccumulative plasticizer. Accumulation of DEHP in the body can eventually cause kidney damage. As a type of natural carotenoid, lycopene (LYC) has a potential protective effect on renal cells, but the protective mechanism has not yet been elucidated. The major goal of this study was to see how effective LYC was at treating DEHP-induced nephrotoxicity in mice. ICR mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) or LYC (5 mg/kg BW/day) for 28 days. Through histopathology and ultrastructure, we found that LYC attenuated DEHP-induced renal tubular cell and glomerular damage. LYC relieved DEHP-induced kidney injury evidenced by lower levels of blood urea nitrogen (Bun), creatinine (Cre), and uric acid (Uric). Meanwhile, the reduced expression of kidney injury molecule-1 (Kim-1) also supported it. Notably, LYC can alleviate the activity or content of cytochrome P450 system (CYP450s) interfered with by DEHP. In addition, LYC treatment reduced nuclear accumulation of DEHP-induced aromatic hydrocarbon receptor (AhR) and AhR nuclear transporter (Arnt), and its downstream target genes such as cytochrome P450-dependent monooxygenase (CYP) 1A1, 1A2, and 1B1 expression significantly decreased to normal in the LYC treatment group. In summary, LYC can mediate the AhR/Arnt signaling system to prevent kidney toxicity in mice caused by DEHP exposure.

Lycopene attenuates di(2-ethylhexyl) phthalate-induced mitophagy in spleen by regulating the sirtuin3-mediated pathway.

Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.

Potential Role of Lycopene in the Inhibition of Di(2-ethylhexyl) Phthalate-Induced Ferroptosis in Spleen Via Modulation of Iron Ion Homeostasis.

Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical and widely used as a plasticizer. Humans can be exposed to DEHP through direct contact or environmental contamination. Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. 140 male mice were assigned into control, vehicle control, Lyc (5 mg/kg BW/d), DEHP (500 and 1000 mg/kg BW/d, respectively), and DEHP + Lyc groups and treated with an oral gavage that lasted 28 d. The ultrastructural results showed that DEHP induced pathological changes and mitochondrial injuries. We further revealed that DEHP exposure destroyed the Fe2+ imbalance homeostasis and, consequently, increases of lipid peroxidation and inhibition of cysteine/glutamate antiporter, all of which were involved in the process of ferroptsis. Moreover, the supplementation of Lyc significantly inhibited the ferroptsis changes mentioned above. Altogether, these results indicated that DEHP exposure triggered splenic cell death via ferroptosis; meanwhile, they also shed new evidence on a potential clue for the intervention and prevention of DEHP-related diseases.