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Background: Previous studies, predominantly in Western individuals, have reported weight gain or weight loss are related to the increased depressive symptoms at all ages, but no study of depressive symptoms has examined its relation to actual (not just self-reported) weight changes in the middle-aged and older adults. Evidence of the relationship in older Asian individuals remains sparse. The study aimed to examine the relationship between weight changes and incidence of depressive symptoms in a nationally representative sample of community-dwelling older Asians. Method: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed both the baseline and follow-up surveys were 3118 for the short-term (two years from 2011–2013) and the long-term (four years from 2011–2015). Additionally, to associate weight change with subsequent depressive symptoms, we also included 2472 participants without depressive symptom in 2013 and observed the incidence of depressive symptom in 2015 (subsequent term from 2013–2015). Finally, weight changes were classified as loss > -3%, stable-3–3%, gain3-6%, gain6-9%, and gain > 9%. Multivariable-adjusted cox regression in the study were used to assess the hazard ratios (HRs) of each weight change category. Results: The incidence of depressive symptoms was 20.72% in the 2011–2013, 27.04% in the 2011–2015, and 23.02% in 2013–2015. Weight loss > 3% for all intervals was associated with higher depressive symptoms than stable weight during the 2011–2013 [1.305(1.031,1.651)] among the total populations. When stratified by sex, the results in males and females were different from those in the total population [females:1.389(0.997, 1.935); males:1.263(0.902, 1.767)]. Weight loss > 3% for intervals was associated with higher depressive symptoms than stable weight during the 2013–2015[1.643(1.140, 2.368)] among the males and its effect was also stronger for the total in 2011–2013. Moreover, there was no significant association between weight gain and incident depressive symptom, and no significant interaction effect in terms of the sex*weight changes. Conclusion: Our findings could inform health promotion interventions to body-weight management aimed at improving the health of the middle-aged and older adults, particularly in the total people with short-term weight loss and males with subsequent term weight loss. [ABSTRACT FROM AUTHOR]

Objectives. To assess the extent of interaction between body mass index (BMI) and triglyceride (TG) level and its effects on blood pressure (BP) in elderly individuals in China. Design. Cross-sectional study. Setting. Data were taken from a cross-sectional study called the China Health and Retirement Longitudinal Study. Participants. The analytic sample included 3629 subjects aged 45 to 96 years. Main Outcome Measurements. Data were obtained from the China Health and Retirement Longitudinal Study, which is a cross-sectional study. Age-adjusted partial Pearson’s correlation test was used to compare various characteristics and BP. Adjusted associations were first used as linear regression models, as appropriate. Then, general linear models adjusted for related potential confounders were used to examine the synergistic effects of BMI and TG level on BP. Finally, a binary logistic regression model adjusted for confounding factors was used to examine the association between BMI or TG level and hypertension. Results. Age-adjusted partial Pearson’s correlation coefficient showed that the TG level was positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both men and women with BMI < 24.0 kg/m2; however, TG level was positively correlated with DBP in women with BMI ≥ 24.0 kg/m2 but not with DBP in men with BMI ≥ 24.0 kg/m2. Multiple linear regression analysis showed that BMI level was significantly and positively associated with both SBP and DBP in men and women with BMI < 24.0 kg/m2, and TG level was significantly and positively associated with SBP in women with BMI < 24.0 kg/m2, independent of other confounding factors. A general linear model analysis with adjustment for confounding factors (age, educational level, marital status, current residence, smoking, eating habits, taking activities, antidiabetic medication, antihypertensive therapy, fasting plasma glucose [FPG], low-density lipoprotein cholesterol [LDL-C], estimated glomerular filtration rate [eGFR], and serum uric acid [SUA]) showed no interaction between BMI and TG level and SBP (men, β = 0.572, P = 0.845; women, β = 0.122, P = 0.923) and DBP (men, β = -0.373, P = 0.810; women, β = 0.272, P = 0.828). A binary logistic regression model analysis with adjustment for confounding factors (age, educational level, marital status, current residence, smoking, drinking, eating habits, taking activities, major accidental injury, physical activity, history of cardiovascular disease, history of liver disease, antilipidemic medication, antidiabetic medication, antihypertensive therapy, FPG, LDL-C, high-density lipoprotein cholesterol [HDL-C], eGFR, and SUA) showed that overweight and obese men and women were more likely to have hypertension (men: odds ratio [OR] = 1.781, 95% confidence interval [CI] = 1.393–2.277; women: OR = 1.653, 95% CI = 1.330–2.055) and women with high TG were more likely to have hypertension (OR = 1.558, 95% CI = 1.219–1.992). Conclusion. An interactive effect of BMI and TG level on BP was not observed in either men or women; however, independent effects of BMI on BP were observed in both men and women, and an association between TG level and hypertension was observed in women. [ABSTRACT FROM AUTHOR]

The NRC selenium (Se) requirement for broiler chicks is 0.15 μg Se/g diet, based primarily on weight gain and feed intake studies reported in 1986. To determine Se requirements in today’s rapidly growing broiler chick, day-old male chicks were fed Se-deficient basal diets supplemented with graded levels of Se (0, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.5, 0.75, and 1.0 μg Se/g) as Na2SeO3 (5/treatment). Diets contained 15X the vitamin E requirement, and there were no gross signs of Se-deficiency. At 29 d, Se-deficient chicks weighed 62% of Se-supplemented chicks; 0.025 μg Se/g reversed this effect, indicating a minimum Se requirement of 0.025 μg Se/g diet for growth for male broiler chicks. Enzyme activities in Se-deficient chicks for plasma GPX3, liver and gizzard GPX1, and liver and gizzard GPX4 decreased dramatically to 3, 2, 5, 10 and 5%, respectively, of Se-adequate levels, with minimum Se requirements of 0.10–0.13 μg Se/g, and with defined plateaus above these levels. Pancreas GPX1 and GPX4 activities, however, lacked defined plateaus, with breakpoints at 0.3 μg Se/g. qPCR measurement of all 24 chicken selenoprotein transcripts, plus SEPHS1, found that SEPP1 in liver, GPX3 in gizzard, and SEPP1, GPX3 and SELK in pancreas were expressed at levels comparable to housekeeping transcripts. Only 33%, 25% and 50% of selenoprotein transcripts were down-regulated significantly by Se deficiency in liver, gizzard and pancreas, respectively. No transcripts could be used as biomarkers for supernutritional Se status. For export selenoproteins SEPP1 and GPX3, tissue distribution, high expression and Se-regulation clearly indicate unique Se metabolism, which may underlie tissues targeted by Se deficiency. Based on enzyme activities in liver, gizzard, and plasma, the minimum Se requirement in today’s broiler chick is 0.15 μg Se/g diet; pancreas data indicate that the Se requirement should be raised to 0.2 μg Se/g diet to provide a margin of safety. [ABSTRACT FROM AUTHOR]

Geomagnetically induced currents (GICs) generated by geomagnetic disturbances (GMD) during strong magnetic storms may trigger chain failures in power systems. In this paper, a critical node identification method based on the improved LeaderRank algorithm considering the effects of geomagnetic storms is proposed. A chain fault identification process based on the fragility theory of complex systems is proposed to determine the initial fault line by critical nodes and simulate the fault development process to obtain the accident chain set. The effectiveness of the method is verified by using the IEEE RTS79 node system as an example. The research results show that the method can reflect the critical nodes and accident chain set of power systems under different geomagnetic storm effects, and the research results can provide a reference for geomagnetic storm disaster quantification, assessment, and prevention. [ABSTRACT FROM AUTHOR]

The present study found that drinking alkaline mineral water confers diarrhea resistance in maternally separated piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis. The improvement in gut microbiota composition and function maintains intestinal epithelial regeneration by activating Wnt/β-catenin signaling to repair damaged intestinal mucosa and interrupted ISC differentiation. This study provides a potential prevention strategy for young mammals at risk of diarrhea. [Display omitted] • Drinking AMC water confers diarrhea resistance in piglets under weaning stress. • Brain-microbe-gut axis is the target of AMC water for diarrhea therapy. • Drinking AMC water alleviates weaning-induced intestinal injury in MS piglets. • Drinking AMC water maintains intestinal epithelial regeneration in MS piglets. • Gut microbe is a key factor in stimulating intestinal stem cell differentiation. Diarrhea has the fourth-highest mortality rate of all diseases and causes a large number of infant deaths each year. The maternally separated (MS) piglet (newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infants. Drinking alkaline mineral water has the potential to be therapeutic in gastrointestinal disorders, particularly diarrhea, but the supporting evidence from system studies and the mechanisms involved have yet to be reported. This study aims to determine whether drinking alkaline mineral water confers diarrhea resistance in MS piglets under weaning stress and what the fundamental mechanisms involved are. MS piglets were used to create a stress-induced intestinal disorder-diarrhea susceptibility model. A total of 240 MS piglets were randomly divided into two groups (6 pens/group and 20 piglets/pen). IPEC-J2 cell line was used for in vitro evaluation. An alkaline mineral complex (AMC) water was employed, and its effect on the hypothalamus-pituitary-adrenocortical (HPA) axis, gut microbes, gut morphology, and intestinal epithelial cell (IEC) proliferation and differentiation were investigated using a variety of experimental methodology. AMC water reduced diarrhea rate in MS piglets by inhibiting the HPA axis, ameliorating gut microbiota structure, and stimulating IEC proliferation and differentiation. Apparently, the brain-microbe-gut axis is linked with AMC water conferring diarrhea resistance in piglets. Mechanistically, AMC water decreased stress hormones (COR and Hpt) secretion by suppressing HPA axis, which then increased the abundance of beneficial gut microbes; accordingly, maintained the proliferation of IEC and promoted the differentiation of intestinal stem cells (ISC) into goblet cell and Paneth cell by activating the Wnt/β-catenin signaling pathway. In the absence of gut microbiota (in vitro), AMC activated the LPS-induced Wnt/β-catenin signaling inhibition in IPEC-J2 cells and significantly increased the number of Lgr5 + cells, whereas had no effect on IPEC-J2 differentiation. Drinking alkaline mineral water confers diarrhea resistance in MS piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis; thus, this study provides a potential prevention strategy for young mammals at risk of diarrhea. [ABSTRACT FROM AUTHOR]

The present study identified a critical role of Cx43 in LYC maintaining BTB integrity, which is a prerequisite for normal spermatogenesis. This study reveals the role of Cx43 in LYC preventing phthalate-induced spermatogenic disorders, and Cx43 regulation may provide the basis for future therapeutic male infertility. [Display omitted] • Phthalate induced spermatogenic disorders and destroyed BTB integrity. • Phthalate caused cell migration capacity decline and cytoskeletal disorganization. • LYC alleviated DEHP-induced disruption of intercellular junctions in mouse testes. • LYC improved DEHP-induced spermatogenic disorders by regulating BTB integrity. • LYC ameliorated DEHP-induced BTB disruption by modulating Cx43 expression. Male infertility is a multifactorial pathological condition and may be a harbinger of future health. Phthalates are ubiquitous environmental contaminants that have been implicated in the global decline in male fertility. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most prevalently used. Lycopene (LYC) is a possible preventive and therapeutic agent for male infertility owing to its antioxidant properties. The blood-testis barrier (BTB) is formed between Sertoli cells where it creates a unique microenvironment for spermatogenesis. We hypothesize that phthalate caused male infertility and LYC plays an important role in phthalate-induced male fertility disorders. Hematoxylin-eosin (H&E) staining, ultrastructure observation, and fluorescence microscopy were used to examine the morphological changes. RNA-Seq, and western blotting were conducted to detect gene and protein levels. Routine testing for sperm morphology and sperm-egg binding assay were conducted to examine the morphological structure and function of sperm. Cell scratch assay and transepithelial electrical resistance (TER) were used to detect cell migration capacity and barrier integrity. In vivo experiments, we showed that LYC prevented DEHP-induced impairment of BTB integrity, which provided a guarantee for the smooth progress of spermatogenesis. LYC improved DEHP-induced change in sperm parameters and fertilization ability. Subsequent in vitro experiments, LYC alleviated MEHP-induced disruption of intercellular junctions in mouse Spermatogonia cells (GC-1 cells) and mouse Sertoli cells (TM4 cells). In MEHP-induced BTB impairment models of Sertoli cells, treatment with LYC or overexpressing connexin-43 (Cx43) promoted cell migration capacity and normalized BTB integrity. Cx43 knockdown inhibited cell migration capacity and perturbed BTB reassembly in LYC preventing DEHP-induced BTB impairment. Our study provides evidence for the role of LYC in phthalates-induced spermatogenic disorders and points to Cx43 as a potential target for male fertility. [ABSTRACT FROM AUTHOR]

Abstract This research employed an in-situ growth method to fabrication of multi-walled nanotubes (MWCNTs)/Fe 3 O 4 electromagnetic absorber. Such a binary material system is featured with good impedance matching behavior and moderate attenuation ability, thus exhibits excellent electromagnetic absorption properties. The results reveal that MWCNTs/Fe 3 O 4 exhibits distinct polarization relaxation phenomenon which inducted by interface polarization. This intensity of interface polarization is tunable by controlling the contact area of Fe 3 O 4 and MWCNTs. Due to the contribution of interface polarization loss behavior, the MWCNTs/Fe 3 O 4 sample achieves a wide band electromagnetic absorption property which the frequency region with RL < −10 dB can covers 5.7 GHz at 1.5 mm. The method of utilizing interface strategy to boost dielectric loss ability has an efficient way to gain wide band electromagnetic absorber. Graphical abstract Image 1 Highlights • MWCNTs/Fe 3 O 4 shows dual magnetic/dielectric loss ability. • The weight ratio of MWCNTs/Fe 3 O 4 is tunable. • The effective frequency of MWCNTs/Fe 3 O 4 was up to 5.7 GHz. [ABSTRACT FROM AUTHOR]

Background: Porcine epidemic diarrhea virus (PEDV) variant strains cause great economic losses to the global swine industry. However, vaccines do not provide sufficient protection against currently circulating strains due to viral mutations. This study traced the molecular characteristics of the most recent isolates in China and aimed to provide a basis for the prevention and treatment of PEDV. Methods: We obtained samples from a Chinese diarrheal swine farm in 2022. Reverse transcription polymerase chain reaction and immunofluorescence were used to determine the etiology, and the full-length PEDV genome was sequenced. Nucleotide similarity was calculated using MEGA to construct a phylogenetic tree and DNASTAR. Mutant amino acids were aligned using DNAMAN and modeled by SWISS-MODEL, Phyre2 and FirstGlance in JMOL for protein tertiary structure simulation. Additionally, TMHMM was used for protein function prediction. Results: A PEDV virulent strain CH/HLJJS/2022 was successfully isolated in China. A genome-wide based phylogenetic analysis suggests that it belongs to the GII subtype, and 96.1–98.9% homology existed in the whole genomes of other strains. For the first time, simultaneous mutations of four amino acids were found in the highly conserved membrane (M) and nucleocapsid (N) proteins, as well as eight amino acid mutations that differed from the vast majority of strains in the spike (S) protein. Three of the mutations alter the S-protein spatial structure. In addition, typing markers exist during strain evolution, but isolates are using the fusion of specific amino acids from multiple variant strains to add additional features, as also demonstrated by protein alignments and 3D models of numerous subtype strains. Conclusion: The newly isolated prevalent strain CH/HLJJS/2022 belonged to the GII subtype, and thirteen mutations different from other strains were found, including mutations in the highly conserved m and N proteins, and in the S1° and COE neutralizing epitopes of the S protein. PEDV is breaking through original cognitions and moving on a more complex path. Surveillance for PEDV now and in the future and improvements derived from mutant strain vaccines are highly warranted. [ABSTRACT FROM AUTHOR]

In the modern poultry industry, newly hatched chicks are unavoidably transported from the hatching to the rearing foster. Stress caused by multiple physical and psychological stressors during transportation is particularly harmful to the liver. Astragalus polysaccharide (APS) possesses multiple benefits against hepatic metabolic disorders. Given that transport stress could disturb hepatic glucolipid metabolism and the role of APS in metabolic regulation, we speculated that APS could antagonize transport stress-induced disorder of hepatic glucolipid metabolism. Firstly, newly hatched chicks were transported for 0, 2, 4, and 8 h, respectively. Subsequently, to further investigate the effects of APS on transport stress-induced hepatic glucolipid metabolism disturbance, chicks were pretreated with water or APS and then subjected to transport treatment. Our study suggested that APS could relieve transport stress-induced lipid deposition in liver. Meanwhile, transport stress also induced disturbances in glucose metabolism, reflected by augmented mRNA expression of key molecules in gluconeogenesis and glycogenolysis. Surprisingly, APS could simultaneously alleviate these alterations via peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)/Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway. Moreover, APS treatment regulated the level of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ), thereby alleviating transport stress-induced alterations of VLDL synthesis, cholesterol metabolism, lipid oxidation, synthesis, and transport-related molecules. These findings indicated that APS could prevent the potential against transport stress-induced hepatic glucolipid metabolism disorders via PGC-1α/SIRT1/AMPK/PPARα/PPARγ signaling system. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is widely used worldwide as a commercial herbicide, Diaminochlorotriazine (DACT) is the main metabolite of ATR in the organism. Both of them disrupt the production of steroids and induce abnormal reproductive development. The granulosa cells (GC s) are important for growth and reproduction of animals. However, the toxicity of ATR on the GCs of birds is not well clarified. To evaluate the effect of the environmental pollutant ATR on bird GCs. The quail GCs were allotted into 7 groups, C (The medium of M199), A20 (20 µM ATR), A100 (100 µM ATR), A250 (250 µM ATR), D20 (20 µM DACT), D100 (100 µM DACT) and D200 (200 µM DACT). The results demonstrated that ATR reduced the viability of GCs, disrupted mitochondrial structure (including mitochondrial cristae fragmentation and the mitochondrial morphology disappearance) and decreased mitochondrial membrane potential. Meanwhile, ATR interfered with the expression of key factors in the steroid synthesis pathway, inducing the secretion of the sex hormones E 2 and P in GCs. which in turn induced apoptosis. Furthermore, the Nrf2/ARE pathway as a potential target to ameliorate ATR-induced endocrine disruption in GCs for proper reproductive functions. Our research provides a new perspective for understanding the effects of ATR on reproductive functions in birds. [ABSTRACT FROM AUTHOR]

Transport stress (TS) not only weakens poultry performance but also affects animal welfare. Additionally, TS can evoke cardiac damage by triggering sterile inflammation in chicks, but the underlying mechanism is not fully understood. Here, we aimed to elucidate how TS induces sterile inflammation and heart injury and to clarify the antagonism effect of astragalus polysaccharides (APS). We randomly divided 60 chicks (one-day-old female) into 5 groups (n = 12): Control_0h (Con_0h) group (chicks were slaughtered at initiation), Control group (stress-free control), TS group (simulated TS exposure for 8 h), TS plus water (TS+W) group, and TS plus APS (TS+APS) group. Before simulation transport, the chicks of TS+W and TS+APS groups were, respectively, dietary with 100 μL of water or APS (250 μg/mL). H&E staining was employed for cardiac histopathological observation. ELISA assay was used to measure oxidative stress marker levels (GSH, GPX, GST, and MDA). A commercial kit was used to isolate the mitochondrial portion, and qRT-PCR was employed to measure the mitochondrial DNA (mtDNA) levels. Furthermore, we evaluated the activity of mtDNA-mediated NF-κB, NLRP3 inflammasome, and cGAS-STING inflammatory pathways and the expression of downstream inflammatory factors by Western Blotting or qRT-PCR. Our findings revealed that APS notably relieved TS-induced myocardial histopathological lesions and infiltrations. Likewise, the decrease in proinflammatory factors (TNF-α, IL-1β, and IL-6) and IFN-β by APS further supported this result. Meanwhile, TS caused severe oxidative stress in the chick heart, as evidenced by decreased antioxidant enzymes and increased MDA. Importantly, APS prevented mtDNA stress and leakage by reducing oxidative stress. Interestingly, TS-induced mtDNA leakage caused a series of inflammation events via mtDNA-PRRs pathways, including TLR21-NF-κB, NLRP3 inflammasome, and cGAS-STING signaling. Encouragingly, all these adverse changes related to inflammation events induced by mtDNA-PRRs activation were all relieved by APS treatment. In summary, our findings provide the first evidence that inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by APS could protect against TS-induced cardiac damage in chicks. [ABSTRACT FROM AUTHOR]

Background: The quality of reporting in systematic reviews (SRs)/meta-analyses (MAs) of diagnostic tests published by authors in China has not been evaluated. The aims of present study are to evaluate the quality of reporting in diagnostic SRs/MAs using the PRISMA statement and determine the changes in the quality of reporting over time. Methods: According to the inclusion and exclusion criteria, we searched five databases including Chinese Biomedical Literature Database, PubMed, EMBASE, the Cochrane Library, and Web of knowledge, to identify SRs/MAs on diagnostic tests. The searches were conducted on July 14, 2012 and the cut off for inclusion of the SRs/MAs was December 31st 2011. The PRISMA statement was used to assess the quality of reporting. Analysis was performed using Excel 2003, RevMan 5. Results: A total of 312 studies were included. Fifteen diseases systems were covered. According to the PRISMA checklist, there had been serious reporting flaws in following items: structured summary (item 2, 22.4%), objectives (item 4, 18.9%), protocol and registration (item 5, 2.6%), risk of bias across studies (item 15, 26.3%), funding (item 27, 28.8%). The subgroup analysis showed that there had been some statistically significant improvement in total compliance for 9 PRISMA items after the PRISMA was released, 6 items were statistically improved regarding funded articles, 3 items were statistically improved for CSCD articles, and there was a statistically significant increase in the proportion of reviews reporting on 22 items for SCI articles (P<0.050). Conclusion: The numbers of diagnostic SRs/MAs is increasing annually. The quality of reporting has measurably been improved over the previous years. Unfortunately, there are still many deficiencies in the reporting including protocol and registration, search, risk of bias across studies, and funding. Future Chinese reviewers should address issues on these aspects. [ABSTRACT FROM AUTHOR]

Propofol, a common intravenous anesthetic, has been found to exert anti-cancer effects with inhibition of cancer cell proliferation, migration and invasion. We tested its possible action against HER2-overexpressing breast cancer cells that developed resistance against trastuzumab. Cell viability assay, ELISA for cytokines, mammosphere formation, quantitative RT-PCR for EMT/IL-6-targeting miRNAs and the in vivo experimental pulmonary metastasis model were performed to understand the epigenetic action of propofol. Propofol sensitized HER2 overexpressing cells to trastuzumab but such action was even more pronounced in resistant cells. Increased cytokines IL-6 as well as IL-8 were released by resistant cells, along with increased mammospheres and induction of EMT, all of which was inhibited by propofol. IL-6 targeting tumor suppressor miR-149-5p was found to be the novel miRNA that was up-regulated by propofol, resulting in the observed effects on cell viability, IL-6 production, mammospheres generation as well as EMT induction. Further, antagonizing miR-149-5p attenuated the propofol effects confirming the epigenetic activity of propofol through miR-149-5p regulation. Finally, in vivo validation in an experimental metastasis model conformed an inhibitory action of propofol against experimental lung metastasis and the essential mechanistic role of miR-149-5p/IL-6 loop. These results present a novel role of general anesthetic propofol against resistant breast cancer cells and the underlying epigenetic regulation of a tumor suppressor miRNA. [ABSTRACT FROM AUTHOR]

Exosomes contain cell-specific collections of bioactive materials including proteins, lipids, and RNAs that are transported to recipient cells to exert their impacts. MicroRNAs (miRNAs) can function as tumor suppressor or oncogenic genes and miR-21 is one of the most frequently up-regulated miRNAs in solid tumors including colon cancer. The aim of this study was to investigate the role of miR-21, secreted from exosomes, in proliferation and invasion of colon cancer, along with the mechanistic details. We used a variety of biochemical techniques including ultracentrifugation-based exosome purification, electron transmission microscopy, western blot and RT-qPCR to detect the expression levels of miR-21 in exosomes purified from culture media of human colonic adenocarcinoma cell lines. We then performed functional and mechanistic studies using three colon cancer cell lines HT29, T84 and LS174 as well as the normal colon epithelial cells CRL1831. miR-21 target PDCD4 was investigated for its role in mediating miR-21 effects. Expression of miR-21 was significantly up-regulated in exosomes of colon cancer cells, compared to the normal human colon epithelial cells. Treatment of colon cancer cells with isolated exosomes or miR-21 led to an increased expression of genes involved in cell proliferation, invasion and extracellular matrix formation. miR-21 targets PDCD4, TPM1 and PTEN were down-regulated by exosomes and silencing of PDCD4 mimicked miR-21 functional effects, even the induced resistance against 5-FU. Our study suggests that targeted inhibition of exosomes, particularly those carrying miR-21, may represent a novel approach for treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a widespread environmental toxicant that severely impacts agricultural production and animal and human health. Nevertheless, DEHP-induced hepatotoxicity at the molecular level in quail remains unexplored. The heat shock response (HSR), involving heat shock proteins (HSPs) and heat shock transcription factors (HSFs), is a highly conserved molecular response that is triggered by stressors, especially exposure to toxicants. To explore the DEHP-induced hepatotoxicity that occurs via regulation of HSR in birds, female quail were dosed with DEHP by oral gavage (0, 250, 500 and 1000 mg/kg) for 45 days. Based on histopathological analysis, the livers of the DEHP-treated groups exhibited structural alterations of hepatocytes, including mitochondrial swelling, derangement of hepatic plates, inflammatory cell infiltration and adipose degeneration. Ultrastructural evaluation of the livers of DEHP-treated quail revealed swollen mitochondria, partial disappearance of mitochondrial membranes and cristae, nuclear chromatin margination and nuclear condensation. The expression of HSF1 and HSF3 significantly decreased after DEHP exposure. The levels of HSPs (HSP10, HSP25, HSP27, HSP40, HSP47, HSP60, HSP70 and HSP90) were significantly downregulated in the livers of DEHP-treated quail. In this study, we concluded that DEHP exposure resulted in liver function damage and hepatotoxicity by reducing the expression of HSFs and HSPs in quail liver, which inhibited the protective effect of the HSR signaling pathway. DEHP can be absorbed by quail via a trophic chain that eventually results in hepatotoxicity. The results of this study indicated that mitochondria are target organelles of DEHP hepatotoxicity. DEHP can activate the HSR signaling pathway and suppress HSP system homeostasis to alleviate mitochondrial dysfunction. The present study provides new insights and shows that DEHP-induced hepatotoxicity is associated with the HSR-mediated defense system. Image 1 • DEHP exposure induced hepatotoxicity. • DEHP triggered the HSR signaling pathway. • DEHP induced hepatotoxicity via suppressing of the HSR signaling pathway. • DEHP exposure resulted in hepatotoxicity via reducing HSPs and HSFs expression. [ABSTRACT FROM AUTHOR]

Abstract Di-(2-ethylhexyl) phthalate (DEHP) in the environment and food chain may impact cerebrum development and neurobehavioral in humans and wildlife. However, it is unclear that DEHP exposure caused cerebral toxicity. This experiment used gavage to expose female quail to 0, 250, 500, and 1000 mg/kg BW/day for 45 days to assess the potential neurotoxicity of DEHP to the cerebrum. It can be observed that there will be obvious neurological abnormalities in the experiment. Cerebrum histological lesions can be observed with HE-staining. Detecting oxidative stress indices, Nrf2 pathway, and mitochondrial dynamics factor, by analyzing the results, these results were observed that DEHP exposure can cause damage to the cerebrum by causing oxidative stress and affecting the balance of mitochondrial dynamics. Nrf2-mediated defense is not activated by exposure to 250 mg/kg DEHP. Nrf2-mediated defense is activated but is not resistant to exposure to medium and high doses of DEHP (500 mg/kg; 1000 mg/kg). DEHP triggers cerebral mitochondrial dysfunction via modulating mitochondrial dynamics. Graphical abstract DEHP exposure causes cerebral toxicity. DEHP causes oxidative stress in the cerebrum. DEHP regulates oxidative stress by activating the Nrf2 defense response. DEHP exposure also triggers disruption of mitochondrial dynamics leading to mitochondrial damage leading to oxidative stress. Image 1 Highlights • DEHP induces the cerebral toxicity. • DEHP activates Nrf2-mediated antioxidant defense in the cerebrum. • DEHP induced cerebral toxicity via disrupting mitochondrial dynamics. • DEHP triggers mitochondrial dysfunction via modulating mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Abstract Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant with endocrine disrupting properties. As a plasticizer, DEHP can be leach from the plastic to transfer the external environment and thus enters the animal food chain, causing serious damage to the animal organs. The heat-shock response (HSR) comprising heat-shock protein (HSPs) and heat-shock transcription factor (HSFs) plays a pivotal role in various toxic stress conditions. For the sake of investigating the effects of DEHP exposure on cardiac toxicity and the regulation of HSR, male quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. Histopathological changes including cardiomyocyte swelling and muscle fiber dilatation were observed in the hearts exposed to DEHP. During the DEHP treatment, the mRNA expression of HSP60 and HSP70 were universally reduced, while the expression of other HSPs (HSP10, HSP25, HSP27, HSP40, HSP47, HSP90, HSP110) had different degrees of growth. In addition, the levels of HSF1, HSF2, and HSF3 were significantly increased. Given the facts above, DEHP exposure induced the toxic effects of quail heart. DEHP exposure did great harm to HSR via affecting the synthesis of HSFs to mediate the transcription of the HSPs. Ultimately, this study provided new evidence that DEHP-induced cardiotoxicity in quail was related to activation of HSR and playing a protective role. Graphical abstract Image 1 Highlights • DEHP exposure induced the renal injury in quail. • DEHP-induced cardiotoxicity is associated with the modulation of HSFs and HSPs. • DEHP exposure activated the HSR pathway responses in the heart. [ABSTRACT FROM AUTHOR]

Abstract Atrazine (ATR) is a most used herbicide which is believed as a pivotal determinant of environmental nephrosis, but potential mechanism is still largely unclear. This study intends to reveal a novel mechanism of ATR-induced nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic indices reflecting the kidney injury were significantly increased in ATR-exposed quail. ATR exposure upregulated the expression of proapoptotic factors (Bax, Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably, cristae of mitochondria decreased, mitochondrial malformation and mitochondrial vacuolar degeneration were observed in ATR-exposed quail. ATR induced the disorder of mitochondrial function related factors expressions and promoted oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2 and Nrf2-target genes. In conclusion, ATR altered the microstructure and function of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction, influencing mitochondrial function related genes expression, modulating Nrf2 signaling pathway. This study suggested ATR induced the nephrotoxicity via disturbing the transcription of mitochondrial function related factors and Nrf2 signaling pathway. Graphical abstract Graphical abstract illustrating the proposed mechanism by ATR-induced nephrotoxicity in quail. Nrf2 signaling pathway was blocked by ATR in kidney of quail. Mitochondria in quail kidney were the target organelles of ATR induced nephrotoxicity. ATR damaged mitochondrial function and morphology. It is deduced that ATR-induced nephrotoxicity is associated with mitochondrial dysfunction and interruption of Nrf2 signaling pathway. Image 1 Highlights • ATR decreased kidney coefficient, impaired histology and function of kidney. • ATR disturbed mitochondrial structure and function related genes expression. • ATR exposure stimulated apoptosis and oxidative stress. • ATR induced variation of Nrf2 signaling pathway and antioxidant response. [ABSTRACT FROM AUTHOR]

Di (2-ethyl hexyl) phthalate (DEHP) as a plasticizer can leach away from the plastic and hence entrances into the animal food chain which caused serious hazard in organs of animals, but there are few studies on DEHP kidney toxicity. The heat-shock response (HSR) consisting of the HSPs and HSFs plays an important role in various toxicity stress conditions. To investigate the influence on kidney toxicity and the modulation of HSR during DEHP exposure, female quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. The shrinkages of glomeruli and dilation of kidney tubule epithelia cells were observed in the kidney of DEHP-exposed quail. DEHP treatment could significantly decrease the expressions of HSP25, HSP27, HSP47, HSP60 , while the expressions of HSP10, HSP40, HSP70, HSP90, HSP110 were upregulated in the kidney. In addition, the expression levels of HSF1 and HSF3 were significantly increased under DEHP. This is the first study to demonstrate quail exposure to DEHP is in fact detrimental to bird kidney. Besides, DEHP could attack HSR by affecting the synthesis of HSFs to mediate the transcription of the HSPs resulting in kidney damage. [ABSTRACT FROM AUTHOR]

Abstract Di (2-ethylhexyl) phthalate (DEHP) is a widely distributed pollutant that is of great concern due to its negative health effects. However, whether DEHP exposure causes liver toxicity in birds remains unclear. To clarify the potential hepatotoxicity of DEHP, quails were exposed to 0, 250, 500 and 1000 mg/kg BW/day DEHP by gavage treatment for 45 days. The livers of DEHP-exposed quails showed histomorphological changes. DEHP exposure induced a significant increase in cytochrome P450 enzyme system (CYP450s) activity (including aniline-4-hydroxylase (AH), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND) and NADPH-cytochrome C reductase (NCR)) and in the contents of total cytochrome P450 (CYP450) and cytochrome b5 (Cyt b5) in quail liver. DEHP exposure also influenced the expression of nuclear xenobiotic receptors (NXRs) and CYP450 isoforms in the liver. The results suggested that DEHP-induced hepatotoxicity in quail liver is associated with activation of the NXRs pathway responses and disruption of CYP450s homeostasis. This study will help to further elucidate DEHP exposure-induced liver toxicity in quails. Graphical abstract DEHP exposure induced hepatic toxicity. DEHP disrupted hepatic CYP450s homeostasis via affecting the transcription of CYPs. DEHP-induced toxicity was associated with activating AHR/PXR/CAR pathway responses and disrupting the CYP450s homeostasis. Image 1 Highlights • DEHP exposure induces the hepatotoxicity in quail. • DEHP triggers the hepatic AHR/PXR/CAR pathway response. • DEHP disrupts the hepatic CYP450 homeostasis. • DEHP modulates the CYPs isoforms transcription via activating the NXRs pathway. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is one of the most extensively used herbicide that eventually leaches into groundwater and surface water from agricultural areas. Exposure to ATR does harm to the health of human and animals, especially the heart. However, ATR exposure caused cardiotoxicity in bird remains unclear. To evaluate ATR-exerted potential cardiotoxicity in heart, quail were exposed with 0, 50, 250, and 500 mg/kg BW/day ATR by gavage treatment for 45 days. Cardiac histopathological alternation was observed in ATR-induced quail. ATR exposure increased the Cytochrome P450s and Cytochrome b5 contents, Cytochrome P450 (CYP) enzyme system (APND, ERND, AH, and NCR) activities and the expression of CYP isoforms ( CYP1B1 , CYP2C18 , CYP2D6 , CYP3A4 , CYP3A7 , and CYP4B1 ) in quail heart. The expression of nuclear xenobiotic receptors (NXRs) was also influenced in the heart by ATR exposure. ATR exposure significantly caused the up-regulation of pro-inflammatory cytokines ( TNF-α, IL-6, NF-κB , and IL-8 ), down-regulation of anti-inflammatory cytokines ( IL-10 ) expression levels and increased NO content and iNOS activity. The present research provides new insights into the mechanism that ATR-induced cardiotoxicity through up-regulating the expression levels of GRP78 and XBP-1s , triggering ER stress, activating the expression of IRE1α/TRAF2/NF-κB signaling pathway related factors ( IRE1α , TRAF2 , IKK , and NF-κB ) and inducing an inflammatory response in quail hearts. In conclusion, ATR exposure could induce cardiac inflammatory injury via activating NXRs responses, disrupting CYP homeostasis and CYP isoforms transcription, altering NO metabolism and triggering ER stress and inflammatory response by activating IRE1α/TRAF2/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a commercially available herbicide that is used worldwide. The intensive use of ATR poses potential risks to animals' and humans' health. Lycopene (LYC) is an anti-oxidative phytochemical that normalizes health hazards triggered by environmental factors. In this study, we aimed to investigate the toxic effects of ATR on the hippocampus and its amelioration by LYC. Male mice were exposed to ATR (50 mg/kg/day or 200 mg/kg/d) and/or LYC (5 mg/kg/d) for 21 days. The results showed that ATR exposure induced hippocampus-dependent learning and memory impairments. ATR-induced ferroptosis in hippocampal cells affects the homeostasis of lipid metabolism, whereas LYC ameliorates the neurotoxic effects of ATR in the hippocampus. LYC inhibited ATR-induced ferroptosis by increasing the expression of HO-1, Nrf2 and SLC7A11. Therefore, this study established that LYC ameliorates ATR-induced spatial learning and memory impairments by inhibiting ferroptosis in the hippocampus and also provides a novel approach for the treatment in contradiction of environmental pollutants. ATR is a kind of herbicide that spreads throughout the environment. Because of its biological activity, particularly antioxidant properties, LYC has attracted a lot of interest. According to our findings, LYC ameliorates ATR-induced spatial learning and memory impairments by inhibiting ferroptosis in the hippocampus of mice. This research may lead to a plausible molecular mechanism for LYC therapy of ATR-induced neurological damage. [Display omitted] • ATR caused spatial learning and memory impairments. • ATR induced ferroptosis in the hippocampus. • LYC can prevent ferroptosis and promote nerve cell repair. • LYC mitigated ATR-induced spatial learning and memory impairments. [ABSTRACT FROM AUTHOR]

Atrazine is well known to be a biologically hazardous substance with toxic effects, but atrazine-induced neurotoxicity remains unclear. The aim of this study was to investigate the mechanisms of atrazine-induced cerebellar toxicity. To determine atrazine-exerted potential neurotoxicity, quails were treated with 50, 250 and 500 mg/kg atrazine by gavage administration for 45 days. Notably, the changes of cytochrome P450 enzyme system (CYP450s) were observed in atrazine-exposed quails. The contents of cytochrome P450 (CYP450) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR), aminopyrin N-demethylase (APND) and aniline-4-hydeoxylase (AH) were increased and erythromycin N-demethylase (ERND) was decreased in quail cerebellum. Nuclear xenobiotic receptors (NXRs) and the transcriptions of NXRs-related target molecules were influenced in cerebellum. Atrazine disrupted the CYP450s balance in quail cerebellum. These results suggested that atrazine-induced cerebellar toxicity in birds was associated with activating PXR/CAR pathway responses and disrupting cytochrome P450 homeostasis. This study provided novel evidences that atrazine exposure induced cerebellar toxicity. [ABSTRACT FROM AUTHOR]

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. DEHP activates xenobiotic-sensing nuclear receptors AHR and CAR signaling pathway, and thereby resulted in lung injury. LYC supplementation is a potential therapeutic strategy to attenuates phthalates-induced lung injury (By Figdraw). [Display omitted] • DEHP causes lung injury via activating AHR/CAR signaling pathway. • DEHP increases the nuclear accumulation of AHR and CAR. • DEHP causes vacuolization and electron density reduced of lamellar bodies. • AHR and CAR can be used as targets for LYC to attenuate DEHP-induced lung injury. [ABSTRACT FROM AUTHOR]

Stress or stress-induced intestinal disturbances, especially diarrhea, are the main triggers for inflammatory bowel disease and irritable bowel syndrome. Diarrhea and intestinal inflammatory disease afflict patients around the world, and it has become a huge burden on the global health care system. Drinking sodium metasilicate-based alkaline mineral water (SM-based AMW) exerts a potential therapeutic effect in gastrointestinal disorders, including gut inflammation, and diarrhea, but the supportive evidence on animal studies and mechanism involved remain unreported. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. This study aims to determine whether drinking SM-based AMW confers diarrhea resistance in maternally separated (MS) piglets under weaning stress and what the underlying mechanisms are involved. 240 newly weaned piglets were randomly divided into the Control group and the sodium metasilicate pentahydrate (SMP) group. A decreased diarrhea incidence was observed in SMP treatment piglets. The intestine injury and activated stress hormones (COR and ACTH) induced by weaning was alleviated by SM-based AMW. This may be related to the improvement of intestinal microflora structure and function by SMP, especially the increase of s_copri abundance. Meanwhile, SMP maintained the integrity of the duodenal mucus barrier in MS piglets. Importantly, by targeting NF-κB inhibition via the microbiota-gut interaction, SM-based AMW alleviated intestinal inflammation, maintained fluid homeostasis by modulating aquaporins and fluid transporter expression, and enhanced barrier integrity by suppressing MLCK/p-MLC signaling. Therefore, drinking metasilicate-based alkaline mineral water confers diarrhea resistance in MS piglets via the microbiota-gut interaction. [Display omitted] • Drinking SM-based AMW confers diarrhea resistance in MS piglets under weaning stress. • Drinking SM-based AMW alleviates intestinal injury in MS piglets. • Drinking SM-based AMW improves the structure of gut microbiota in MS piglets. • Anti-diarrhea effect of SM-based AMW is related to microbiota-gut interaction. • s_copri is the key community of SM-based AMW mediated microbiota-gut interaction. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a widely used herbicide with biologically toxic effects that can lead to neurotoxicity. Lycopene (LYC) is an antioxidant with chemoprotective properties. However, little know about the mechanisms of preventative interventions about LYC alleviated ATR-induced neurotoxicity. Male mice were treated with distilled water (C), 5 mg/kg BW/day LYC (L), 50 and 200 mg/kg BW/day ATR (A1, A2), respectively and LYC + ATR (A1+L, A2+L). ATR promoted oxidative stress and inflammatory damage, as showed by the effects on MDA, H 2 O 2 , IL-6 and TNF-α accumulation, and IL-10, SOD, CAT and GSH depletion, which caused neuronal swelling and mitochondrial vacuolar degeneration. ATR disrupted the CYP450s balance via increasing contents of CYP450 and cytochrome B5, enhancing activities of NCR and ERND and activating NXRs and NXRs-related transcription factors. However, all these effects were reversed by LYC pretreatment. Collectively, these data indicated that LYC inhibited ATR-induced oxidative damage through modulating xenobiotic-sensing nuclear receptors and CYP450s. [Display omitted] • LYC inhibits ATR exposure-induces neurotoxicity. • LYC alleviates ATR exposure-induces AHR/PXR/CAR pathway responses. • LYC alleviates ATR-induces the CYP450 homeostasis disorders and CYPs transcription. • LYC alleviates ATR exposure triggers oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

As one of the most used phthalates, Di (2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant. Extremely persistent plastic can enter the food chain of animals through the aquatic environment, affect metabolic pathways and cause damage to the digestive system. But the molecular mechanism of its toxic effects on the duodenum in birds has not been elucidated. To investigate the toxicity of phthalates in the duodenum, quails were gavaged with 250, 500, and 750 mg/kg doses of DEHP for 45 days, and water and oil control groups were retained. This study revealed that subchronic exposure to DEHP could lead to duodenal barrier defect in quail. The damage to duodenum was reflected in a reduction in V/C and tight junction proteins. Moreover, DEHP also led to a breakdown of antimicrobial defenses through the flora derangement, which acted as a biological barrier. The massive presence of Lipopolysaccharide (LPS) led to the activation of TLR4 receptors. In addition, DEHP activated oxidative stress, which synergized the inflammatory response induced by the TLR4-NFκB pathway, and further promoted duodenum damage. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction. DEHP (a commonly used phthalate) induced duodenal barrier defect and flora derangement of quail, which is sensitive to environmental pollutants. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction. [Display omitted] • Duodenal barrier defect disrupts microbiota-barrier-immune interaction. • DEHP causes duodenal flora derangement and dysbiosis of antimicrobial function. • Duodenal Proteobacteria increased most significantly after DEHP treatment. • DEHP induces duodenum damage and decreases V/C in quail. • DEHP activates duodenal oxidative stress and inflammation in quail. DEHP (a commonly used phthalate) is ubiquitous in the environment due to overuse. This study could warn of the health risks to animals exposed to phthalates and even humans. [ABSTRACT FROM AUTHOR]

As a plasticizer, di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract. [Display omitted] • DEHP increases the damage severity grade and decreases the villus length/crypt depth. • DEHP-induced jejunal toxicity is associated with oxidative stress in quail. • DEHP destroys the steady state of the NXR and CYP response in the quail jejunum. • DEHP activates Nrf2-mediated antioxidant defense in the quail jejunum. [ABSTRACT FROM AUTHOR]

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. Exposure to persistent environmental pollutants such as di(2-ethylhexyl) phthalate (DEHP) has been involved in multiple health disorders, including splenic diseases. In this study, we clarified the potential protective effect of lycopene on DEHP-induced splenic injury. The results showed that Lyc inhibited DEHP induced oxidative damage by regulating the P62-Keap1-NRF2 signaling pathway, indicating that Lyc could alleviate the toxic effects of DEHP and may be helpful in reducing spleen injury. [Display omitted] • Lyc alleviated DEHP exposure-induced splenic injury. • Lyc alleviated the DEHP exposure-induced redox imbalance. • Lyc mitigated the inhibition of P62-Keap1-NRF2 pathway induced by DEHP exposure. • Lyc alleviated the splenic cell mitochondrial injuries induced by DEHP exposure. [ABSTRACT FROM AUTHOR]

Transport stress (TS) not only affects animal welfare but also eventually leads to higher morbidity and mortality. Moreover, TS could induce heart injury in animals, but the possible mechanism has yet to be fully explored. Astragalus polysaccharide (APS) is a main active component of Radix Astragali , which has an extensive anti-stress effect. However, the effect of APS on TS-induced heart injury has not yet been elucidated. In this study, a chick model of simulated TS was used. 240 newly hatched chicks were arranged into 4 groups: Control (Con), Transport group (T), Transport + water group (TW), and Transport + APS group (TA). Before transport, the chicks of the TW and TA groups were treated with deionized water and APS (0.25 mg/mL, 100 µL) by oral drops respectively. The histopathological analysis of myocardial tissue was assessed by hematoxylin and eosin staining. qRT-PCR and Western Blotting assays were employed to measure the expression of genes and proteins. Semiquantitative PCR was performed for the X box-binding protein-1 (XBP-1) mRNA splicing assay. The results indicated that APS significantly reduced TS-induced myocardial histopathological changes. Meanwhile, TS induced endoplasmic reticulum stress (ERS), evidenced by an activation of the unfolded protein response (UPR) signaling pathway and up-regulation of ERS-markers (P < 0.05). Moreover, TS markedly triggered autophagy induction by activating AMP-activated protein kinase (AMPK), reflected by augmented LC3-II/LC3-I, AMPK phosphorylation and autophagy-related genes (ATGs) expression (P < 0.05). Importantly, our study manifested that treatment of APS could reduce TS-induced ERS and AMPK-activated autophagy, accordingly alleviating heart injury of transported chicks. In summary, these findings indicate that TS induces heart injury in chicks via an ERS-UPR-autophagy-dependent pathway, and APS as an effective therapeutic method to alleviate it. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether closed suction drainage ( CSD) is associated with early recovery of knee function in patients undergoing total knee arthroplasty ( TKA). Methods Between January 2015 and September 2015, 80 consecutive patients were prospectively randomized into two groups: a CSD group (40 cases; average age, 66.9 ± 8.6 years; male, 8; female, 32) and a non- CSD group (40 cases; average age, 66.8 ± 10.1 years; male, 9; female, 31). Local inflammation outcomes (assessed by a visual analog scale [ VAS], swelling and skin temperature), calculated total blood loss ( CBL), hidden blood loss ( HBL), blood transfusion requirements and hemoglobin concentrations were recorded. Hospital for Special Surgery ( HSS) knee scores, range of motion ( ROM), limb swelling, tension vesicles, ecchymosis, time to regaining straight leg raising and duration of hospital stay were documented. All surgeries were performed by the same surgeon and followed up for 3 months. Results The peri-wound skin temperature and knee VAS pain scores were lower in the non- CSD group. Patients in the non- CSD group had significantly better knee ROM ( P = 0.028). The time to regaining active straight leg raising was significantly shorter in the non- CSD group N than in the CSD group ( P = 0.014). In addition, patients in the non- CSD group had a shorter length of hospital stay ( P = 0.004) than those in the CSD group, indicating earlier recovery of knee function. HBL was significantly less in the CSD group than the non- CSD group ( P = 0.006) on postoperative day ( POD) 5. However, CBL did not differ significantly between the two groups on POD5. There were no significant differences between two groups in all other assessed variables. Conclusion In this randomized study, primary TKA without CSD was associated with faster recovery related to less local inflammation and better early knee function. Furthermore, use of a drain had no significant advantage with respect to other outcome measures and may have increased costs. Based on these data, CSD after primary TKA is not routinely indicated. [ABSTRACT FROM AUTHOR]

Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR / SREBP-1c and PPARα / γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines (NF-κB , IL-6 , IL-8 , IL-1β , and TNF-a). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR / SREBP-1c / PPARα / γ and NF-κB signaling pathways. This research showed that DEHP could induce lipid metabolism disorder and inflammatory response via LXR / SREBP-1c / PPARα / γ / NF-κB signal pathways. This study provides new evidence for the mechanisms of DEHP-induced hepatotoxicity. [Display omitted] • DEHP exposure caused hepatotoxicity. • DEHP induced lipid metabolism disorders in liver. • DEHP disrupted lipid metabolism to induce lipotoxicity in liver. • DEHP exposure caused inflammation response in liver. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in agricultural and industrial plastic products. Many researchers have demonstrated that DEHP can cause varying degrees of harm to the heart. This research investigated the mechanism by which DEHP causes heart damage in quail. The quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day or 750 mg/kg BW/day) for 45 days. The present study suggested that DEHP could cause varying levels of heart damage, including disordered myocardial fiber arrangements, myocardial fiber breakage and myocardial cell swelling. The results showed that DEHP induced mitochondrial damage, such as cavitation lesions and mitochondrial crest breakage. DEHP damaged mitochondria and inhibited nuclear respiratory factor 1 (Nrf1)-mediated mitochondrial biogenesis, which led to mitochondrial damage. DEHP caused oxidative stress in the heart and activated the defense mechanism of the nuclear factor red blood cell 2 related factor 2 (Nrf2) system. DEHP-induced mitophagy was related to a decline in mitochondrial biogenesis and disordered mitochondrial dynamics. The data indicated that DEHP exposure damaged cardiac mitochondria and caused mitophagy and cardiotoxicity. Of note, this study showed that DEHP-induced mitophagy and mitochondrial damage are associated with the dysregulation of mitochondrial biogenesis. This study showed that DEHP exposure can cause cardiotoxicity, which was closely related to mitochondrial damage. DEHP inhibited Nrf1-mediated mitochondrial biogenesis and caused an imbalance in mitochondrial dynamics. DEHP exposure increased the level of Nrf2 because it induced oxidative stress and activated the Nrf2 signaling pathway. DEHP-induced mitochondrial damage leads to the occurrence of mitophagy, which ultimately leads to cardiotoxicity. This study provided new evidence for the effect of DEHP on the cardiotoxicity of quail. [Display omitted] • DEHP caused an Nrf1-mediated decline in mitochondrial biogenesis. • DEHP-induced cardiac oxidative stress damage activates the Nrf2 signaling pathway. • DEHP caused disordered mitochondrial dynamics in the heart of quail. • DEHP-induced mitophagy was associated with reduced mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is one of the toxic environmental heavy metals that poses health hazard to animals due to its toxicity. Nano-Selenium (Nano-Se) is a Nano-composite form of Se, which has emerged as a promising therapeutic agent for its protective roles against heavy metals-induced toxicity. Heat shock proteins (HSPs) play a critical role in cellular homeostasis. However, the potential protective effects of Nano-Se against Cd-induced cerebellar toxicity remain to be illustrated. To investigate the toxic effects of Cd on chicken's cerebellum, and the protective effects of Nano-Se against Cd-induced cerebellar toxicity, a total of 80 male chicks were divided into four groups and treated as follows: (A) 0 mg/kg Cd, (B) 1 mg/kg Nano-Se (C) 140 mg/kg Cd + 1 mg/kg Nano-Se (D) 140 mg/kg Cd for 90 days. We tested heat shock protein pathway-related factors including heat shock factors (HSFs) HSF1, HSF2, HSF3 and heat shock proteins (HSPs) HSP10, HSP25, HSP27, HSP40, HSP60, HSP70 and HSP90 expressions. Histopathological results showed that Cd treatment caused degradation of Purkinje cells. In addition, HSFs and HSPs expression decreased significantly in the Cd group. Nano-Se co-treatment with Cd enhanced the expression of HSFs and HSPs. In summary, our findings explicated a potential protective effect of Nano-Se against Cd-induced cerebellar injury in chicken, suggesting that Nano-Se is a promising therapeutic agent for the treatment of Cd toxicity. Cd can be absorbed to chickens through the food chain, eventually caused cerebellar injury. However, Nano-Se attenuated cerebellar injury induced by Cd. This study indicated that the cerebellum is the target organ of Cd-induced cerebellar injury. Chronic and high-dose Cd treatment caused blurring nucleolus and degradation of Purkinje cell. In addition, HSFs and HSPs expression were decreased significantly, However, supplementation of Nano-Se exerts protective function against chronic Cd-induced cerebellar injury through activating heat shock protein pathway. [Display omitted] • Cerebellum is the target organ of Cd toxicity. • Cd inhibited heat shock protein pathway in cerebellum. • Nano-Se activated the heat shock protein pathway that alleviated cerebellar injury. • Nano-Se is a promising candidate for the treatment of Cd toxicity. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has been implicated in the pathogenesis of inflammation, myocardial infarction, angiocardiopathy, even cancers. However, it is unknown that Cd-induced cardiac toxicity through Nrf2-mediate antioxidant defense and Cytochrome P450 (CYP450) system. To ascertain the chemoprevention of Cd-induced cardiac toxicity, total 60 newborn chicks were fed with different doses of Cd (0 mg/kg, 35 mg/kg and 70 mg/kg) for a period of 90 days feed administration. Results indicated Cd exposure caused cardiac histopathology changed and functions abnormal, induced NOS activities raised and cardiac inflammation, triggering inflammation factors (IL-6, IL-8, TNF-α, and NF-κb) upregulation and inhabitation of IL-10. Cd caused increase of total CYP450 and Cytochrome b 5 (Cyt b 5) contents, while erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR) indicated opposite situations with different degrees of reduction in microsomes. The mRNA level of most CYP450s isoforms (CYP1A1, CYP1A2, CYP1A5, CYP1B1, CYP2C18, CYP2C45, CYP3A4, CYP3A7 and CYP3A9) were significantly increase but CYP2D6 expression level changed not obvious. Furthermore, Cd treatment caused increased the peroxidation product (MDA) and H 2 O 2 over accumulation, the decreased of T-AOC accompanied by decreased activity of antioxidant enzymes (T-SOD, GST and GPX). Over accumulation of Cd lead to oxidative stress and activated Nrf2 signal pathway through upregulating pivotal target genes (HO-1, NQO1, GCLC, GCLM and SOD). These findings suggested Cd exposure caused cardiotoxicity through CYP450s enzymes homeostasis disturbance and Nrf2-mediated oxidative stress signal pathways defense. These results may provide new evidence on molecular mechanism of Cd-induced cardiac toxicity. Cadmium (Cd) enters the heart through cell membranes and disrupts the metabolic system. Findings from the present study provide new evidence that Cd exposure affects the modulation of Cytochrome P450 Systems and Nrf2 mediated antioxidant defense in the heart. Cd exposure resulted in oxidative stress via disrupting the homeostasis of CYP450s, activating Nrf2 signaling. All data supplied in the present study contribute to broadening knowledge on the mechanisms of Cd-induced cardiotoxicity. Image 1 • Cadmium exposure caused cardiotoxicity. • Cadmium induced cardiac inflammation. • Cadmium disturbed the Cytochrome P450 homeostasis in heart. • Cadmium induced oxidative stress via affecting Nrf2 mediated antioxidant defense. [ABSTRACT FROM AUTHOR]

A dual-function probe BHMH was synthesized and characterized functioned with benzothiazole as signal unit for the simultaneous detection of Zn2+ and Al3+ DMF/H 2 O (1/1, v/v, 0.01 M HEPES, pH = 6.0). Probe BHMH achieved in the recognition of Zn2+ and Al3+ both through obvious fluorescence turn-on and absorbance ratiometric response. The limit of detection (LOD) according to the titration of fluorescence for Zn2+ and Al3+ were 1.27 × 10−7 M and 1.42 × 10−7 M, respectively. Furthermore, the significant color changes could be detected by naked eye whatever under ultraviolet-lamp or daylight. According to Job plot, the binding ratio of BHMH with Zn2+ and Al3+ were determined as 1:1 and 2:1, respectively. The binging detail was further confirmed by 1H NMR titration and ESI-MS analysis as well. Moreover, probe BHMH was successfully applied in the detection Zn2+ and Al3+ in real sample and test stripe. Unlabelled Image • Chemosensor BHMH with benzothiazole fluorophore was synthesized and characterized. • BHMH exhibits highly selective to Zn2+ and Al3+ with significant fluorescence turn-on and color change. • Limit of detection (LOD) for Zn2+ and Al3+ were all reached the level of 10−8 M. • BHMH was successfully applied in the detection of Zn2+ and Al3+ in test paper. [ABSTRACT FROM AUTHOR]

Metastasis is regarded as the fatal hallmark for colon cancer, but molecular mechanisms responsible for it have remained poorly defined. Glucocorticoid receptor (GR) within the tumor microenvironment mediates the effects of stress hormones which are used in clinics for their inflammation-modulatory and immunosuppressive properties. Further, epigenetic activation of GR promotes tumor heterogeneity and metastasis. Here, we sought to investigate the correlation between GR activation and proliferation and invasion in metastatic colon cancer microenvironment. We used proliferation/invasion assays, western blot, RT-qPCR, immunofluorescence staining and quantitative methylation to study glucocorticoid-GR signaling, including the involvement of CDK1, in human colon adenocarcinoma cell lines HT29 and T84 (a representative metastatic cell line). Nuclear expression levels of GR were significantly upregulated in metastatic T84 cells, and glucocorticoid derivative, dexamethasone (DEX) treatment caused increased proliferation and invasion in T84 cell, compared to HT29 cell. DEX treatment induced CDK1 expression which was accompanied by reduced CDK1 methylation, indicating epigenetic regulation. Depletion of GR suppressed proliferation of metastatic colon carcinoma cells and depletion of CDK1 had similar suppressing effects on proliferation as well as invasion of metastatic cells. Our study suggests that glucocorticoid-GR-CDK1 signaling induces proliferation and invasion of colon cancer cells and therapies involving the use of glucocorticoids need to exercise caution and re-evaluation. [ABSTRACT FROM AUTHOR]

Background: In endemic areas, placental malaria due to Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive.Methods and Findings: During 2002-2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery ("PM-negative"), offspring of mothers with placental malaria at delivery ("PM-positive") were 41% more likely to experience their first parasitemia at a younger age (adjusted hazard ratio [AHR] = 1.41, 95% confidence interval [CI] 1.01-1.99). The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy (adjusted odds ratio [AOR] = 0.67, 95% CI 0.50-0.91) than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds (AOR = 0.21, 95% CI 0.09-0.47). In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia (AOR = 1.59, 95% CI 1.16-2.17).Conclusion: Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring. [ABSTRACT FROM AUTHOR]