Patulin Induces Acute Kidney Injury in Mice through Autophagy-Ferroptosis Pathway.

Patulin (PAT) is a common mycotoxin, widely found in cereals, seafood, nuts, and especially in fruits and their products. Exposure to this mycotoxin has been reported to induce kidney injury. However, the possible mechanism remains unclear. In our study, short-term high-dose intake of PAT caused acute kidney injury (AKI) in mice. We performed high-throughput transcriptional sequencing to identify differentially expressed genes (DEGs) between the treatment and control groups. The ferroptosis signaling pathway had the highest enrichment, suggesting ferroptosis is involved in PAT-induced AKI. Further, the existence of ferroptosis and autophagy was confirmed by observing the changes of mitochondria morphology and the formation of autophagosomes by electron microscopy. And the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), p62, nuclear receptor coactivator 4 (NCOA4), and ferritin heavy chain 1 (FTH1) were downregulated, whereas acyl-CoA synthase long-chain family member 4 (ACSL4), transferrin (TF), LC3, and ferritin light chain (FTL) expression were upregulated in PAT-exposed mice. These results suggested autophagy-dependent ferroptosis occurred in the animal model. This view has also been confirmed in the human renal tubular epithelial cell (HKC) experiments. Autophagy inhibitor 3-methyladenine (3MA) attenuated PAT-induced ferroptosis and the iron contents in HKC cells. Simultaneous autophagy-dependent ferroptosis can be inhibited by ferroptosis inhibitors ferrostatin-1 (Fer-1) and desferrioxamine (DFO). In general, this study provides a new perspective for exploring the new mechanism of acute kidney injury caused by PAT.

LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. METHODS: Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. RESULT: Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting ß-TrCP1 mediated ubiquitin degradation of ß-catenin proteins, which in turn causes enhanced tumorigenesis. CONCLUSIONS: Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.

Analysis of the Coptis chinensis genome reveals the diversification of protoberberine-type alkaloids.

Chinese goldthread (Coptis chinensis Franch.), a member of the Ranunculales, represents an important early-diverging eudicot lineage with diverse medicinal applications. Here, we present a high-quality chromosome-scale genome assembly and annotation of C. chinensis. Phylogenetic and comparative genomic analyses reveal the phylogenetic placement of this species and identify a single round of ancient whole-genome duplication (WGD) shared by the Ranunculaceae. We characterize genes involved in the biosynthesis of protoberberine-type alkaloids in C. chinensis. In particular, local genomic tandem duplications contribute to member amplification of a Ranunculales clade-specific gene family of the cytochrome P450 (CYP) 719. The functional versatility of a key CYP719 gene that encodes the (S)-canadine synthase enzyme involved in the berberine biosynthesis pathway may play critical roles in the diversification of other berberine-related alkaloids in C. chinensis. Our study provides insights into the genomic landscape of early-diverging eudicots and provides a valuable model genome for genetic and applied studies of Ranunculales.

Anti-nociceptive effect of Portulaca oleracea L. ethanol extracts attenuated zymosan-induced mouse joint inflammation via inhibition of Nrf2 expression.

The aim of this study was to explore the effects of ethanol extracts from Portulaca oleracea L. (ePO) on joint inflammation and to explain the underlying mechanisms. A joint inflammation mouse model was constructed by injecting zymosan, and the Von Frey method was employed and the joint thickness measured. The numbers of leukocytes, neutrophils, and monocytes were counted in the joint cavity and the infiltration of inflammatory cells was assessed by joint histopathological analysis. The mRNA levels of inflammatory cytokines were determined by quantitative RT-PCR and their secretion levels were determined by specific ELISAs. Pre-treatment with ePO inhibited articular mechanical hyperalgesia and edema and ameliorated the recruitment of mononuclear neutrophils and leukocytes. In addition, pre-treatment with ePO improved pathological alternations in the joint tissues by reducing the number of inflammatory cells. Pre-treatment with ePO regulated the nuclear factor erythroid 2-related factor 2 (Nrf2)-related proteins and thereby inhibited oxidative stress. In addition, ePO inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome-related genes (NLRP3, ASC, pro-caspase-1 and pro-IL-1ß), modulated inflammatory cytokines and the activation of NF-κB. ePO attenuated zymosan-induced joint inflammation by regulating oxidative stress, NLRP3 inflammasome, and NF-κB.

Evaluation of current medical approaches for COVID-19: a systematic review and meta-analysis.

BACKGROUND: Because of the lack of vaccination, it is urgent to find effective antiviral agents for COVID-19 treatment. METHOD: Online databases were searched for articles published before or on 22 June 2020. Studies reporting the effectiveness and safety of antiviral agents for COVID-19 were analysed. RESULTS: A total of 42 studies were included in this analysis. Hydroxychloroquine (HCQ) was not associated with the incidence of death (risk ratio (RR)=1.08; 95% CI 0.81 to 1.44) and severe cases (RR=1.05; 95% CI 0.61 to 1.81). Patients treated with HCQ obtained few benefits with respect to the clearance of viral RNA and were more likely to have adverse reactions. HCQ treatment could shorten the body temperature recovery time (weighted mean difference = -1.04; 95% CI -1.64 to -0.45). Lopinavir/ritonavir (LPV/r) (RR=0.90; 95% CI 0.76 to 1.07) and Arbidol (RR=1.09; 95% CI 0.92 to 1.29) were not associated with the negative conversion rate. Integrative Chinese-Western medicine alleviated clinical symptoms and decreased the incidence of severe cases (RR=0.38; 95% CI 0.25 to 0.59). Remdesivir treatment reduced the 14-day mortality rate of patients with severe COVID-19 (RR=0.64; 95% CI 0.44 to 0.94). Convalescent plasma (CP) tended to increase the negative conversion rate (RR=2.47; 95% CI 1.70 to 3.57). CONCLUSION: HCQ, LPV/r and Arbidol bring little benefit in COVID-19 treatment. Integrative Chinese-Western medicine improved the clinical symptoms of patients with COVID-19. Remdesivir and CP might be the potential treatments for patients with severe COVID-19. However, large-scale clinical randomised trials are needed to validate our conclusions.

Pancreatic cancer cell apoptosis is induced by a proteoglycan extracted from Ganoderma lucidum.

The Traditional Chinese Medicine, Ganoderma lucidum, has been widely used for its immunity-related and anti-cancer effects. Fudan-Yueyang-Ganoderma lucidum (FYGL) is a proteoglycan, extracted from Ganoderma lucidum, that has shown safe anti-diabetic activity in vivo. The present study demonstrated that FYGL could selectively inhibit the viability of PANC-1 and BxPC-3 pancreatic cancer cells in a dose dependent manner, but not in Mia PaCa-2 pancreatic cancer cells and HepG2 liver cancer cells. In addition, FYGL could inhibit migration and colony formation, and promote apoptosis in PANC-1 cells, but not in Mia PaCa-2 cells. Further investigation into the underlying mechanism revealed that FYGL could inhibit the expression level of the Bcl-2 protein in PANC-1 cells, but not in Mia PaCa-2 cells, leading to an increase in reactive oxygen species (ROS) and a reduction in the mitochondrial membrane potential and cell apoptosis. The increased ROS also promoted the formation of autophagosomes, along with an increase in the microtubule-associated protein light chain 3 II/I ratio. However, FYGL halted autophagy by preventing the autophagosomes from entering the lysosomes. The inhibition of autophagy increased the accumulation of defective mitochondria, as well as the production of ROS. Taken together, the processes of ROS regulation and autophagy inhibition promoted apoptosis of PANC-1 cells through the caspase-3/cleaved caspase-3 cascade. These results indicated that FYGL could be potentially used as an anti-cancer agent in the treatment of pancreatic cancer.

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells.

CONTEXT: The Chinese herbal formula Heshouwu decoction (Heshouwuyin) has protective effects on testicular function in aging male rats, but the mechanism is unknown. OBJECTIVE: This study investigated whether Heshouwuyin affects the testicular function of aging rats by regulating the insulin/IGF signalling pathway. MATERIALS AND METHODS: Sixteen-month-old male Wistar rats in the Heshouwuyin group and the natural-aging group were orally administered Heshouwuyin granules (0.056 g/kg) or equivalent normal saline for 60 d. The testicular tissue of 12-month-old male Wistar rats was removed as a young control group (n = 10). The testicular tissue and spermatogenic cells were studied. RESULTS: The immunofluorescence results revealed that the insulin receptor (INSR)- (0.056 ± 0.00548), insulin receptor substrate 1(IRS1)- (0.251 ± 0.031), IRS2 (0.230 ± 0.019)- and insulin-like growth factor 1 (IGF1)-positive cell rate (0.33 ± 0.04) in the aging group was higher than that in the young control group (0.116 ± 0.011, 0.401 ± 0.0256, 0.427 ± 0.031, 0.56 ± 0.031; p < 0.01), and the IGF-binding protein 3 (IGFBP3)-positive cell rate (0.42 ± 0.024) was lower than that (0.06 ± 0.027) in the young group (p < 0.01). The intervention of Heshouwuyin reversed the above phenomena. The qPCR and immunoblot results were consistent with those of the immunofluorescence. The same results were obtained in spermatogenic cells. CONCLUSIONS: Our research shows that Heshouwuyin can regulate the insulin/IGF signalling pathway to improve testicular function, and provides an experimental basis for further clinical use.

Mechanism of Heshouwuyin inhibiting the Cyt c/Apaf-1/Caspase-9/Caspase-3 pathway in spermatogenic cell apoptosis.

BACKGROUND: The Chinese herbal compound Heshouwuyin has been shown to downregulate the apoptotic rate of testicular tissue cells in Wistar naturally aging rats, and this effect might be related to the mitochondrial pathway [15]. Apoptotic protease activating factor-1 (Apaf-1) is a major component of the apoptotic complex, which is a key element of the mitochondrial endogenous apoptotic pathway [13]. To further clarify the mechanism of Heshouwuyin in the mitochondrial apoptotic pathway, this study used Apaf-1 as a target to explore the mechanism by which Heshouwuyin inhibits the Apaf-1 pathway of spermatogenic cell apoptosis. METHODS: In this study, an aging model of rat spermatogenic cells was established using free radical oxidative damage. Flow cytometry was used to detect the apoptosis rate of germ cells and the inhibitory effect of Heshouwuyin. Apaf-1 was specifically knocked down by siRNA interference technology, and mitochondrial membrane potential was measured. qRT-PCR, Western blotting and immunofluorescence analyses were used to detect the expression of the key genes Cyt c, Caspase-9 and Caspase-3 in the mitochondrial apoptotic pathway of spermatogenic cells. RESULTS: Heshouwuyin reduced the mRNA and protein expression levels of Cyt c, Caspase-9 and Caspase-3 in senescent spermatogenic cells. In these cells, the mRNA and protein expression levels of Cyt c did not change significantly after specific knockdown of Apaf-1, and the mRNA and protein expression levels of Caspase-9 and Caspase-3 decreased significantly. This finding indicated that knockdown of Apaf-1 could decrease the mRNA and protein expression levels of the downstream pro-apoptotic genes Caspase-9 and Caspase-3. Although Cyt c was an upstream gene of Apaf-1, knockdown of Apaf-1 had no significant effect on Cyt c expression. CONCLUSION: The inhibition of spermatogenic cell apoptosis by Heshouwuyin was closely related to the Cyt c/Apaf-1/Caspase-9/Caspase-3 pathway. The inhibition of apoptosis by Heshouwuyin not only involved the Apaf-1 pathway, but other signaling pathways.

Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes) Polysaccharides Suppress Tacrine-induced Apoptosis by ROS-scavenging and Mitochondrial Pathway in HepG2 Cells.

Tacrine is the first drug licensed for the treatment of Alzheimer disease. Unfortunately, reversible hepatotoxicity limits its clinical use. In our previous study, we found that tacrine induced apoptosis in HepG2 cells by reactive oxygen species (ROS) formation and mitochondria dysfunction. Inonotus obliquus is a mushroom traditionally used as a folk medicine in Asia. In this study, the possible protective effect of polysaccharides from I. obliquus was investigated. The results showed that I. obliquus polysaccharides (IOP) reduced tacrine-induced apoptosis in HepG2 cells. Inhibition of tacrine-induced ROS generation, 8-OHdG formation in mitochondrial DNA, and loss of the mitochondrial transmembrane potential by IOP were also observed. Furthermore, IOP decreased the cytochrome c release and activation of caspase-3 induced by tacrine. These data suggest that IOP could inhibit tacrine-induced apoptosis in HepG2 cells. The protection is mediated by an antioxidant protective mechanism. Consumption of IOP may be a plausible way to prevent tacrine-induced hepatotoxicity.

Citreoviridin induces myocardial apoptosis through PPAR-γ-mTORC2-mediated autophagic pathway and the protective effect of thiamine and selenium.

Citreoviridin (CIT), a mycotoxin and ATP synthase inhibitor, is regarded as one of aetiology factors of cardiac beriberi and Keshan disease. Thiamine (VB1) and selenium (Se) improve the recovery of these two diseases respectively. The underlying mechanisms of cardiotoxic effect of CIT and cardioprotective effect of VB1 and Se have not been fully elucidated. In this study, we found that ectopic ATP synthase was more sensitive to CIT treatment than mitochondrial ATP synthase in H9c2 cardiomyocytes. CIT inhibited the transcriptional activity of peroxisome proliferator activated receptor gamma (PPAR-γ) in mice hearts and H9c2 cells. PPAR-γ agonist attenuated the inhibitory effect of CIT on mechanistic target of rapamycin complex 2 (mTORC2) and stimulatory effect of CIT on autophagy in cardiomyocytes. CIT induced apoptosis through lysosomal-mitochondrial axis in cardiomyocytes. PPAR-γ agonist and autophagy inhibitor alleviated CIT-induced apoptosis and accelerated cardiac biomarker. VB1 and Se accelerated the basal transcriptional activity of PPAR-γ in mice hearts and H9c2 cells. Furthermore, VB1 and Se reversed the effect of CIT on PPAR-γ, autophagy and apoptosis. Our findings defined PPAR-γ-mTORC2-autophagy pathway as the key link between CIT cardiotoxicity and cardioprotective effect of VB1 and Se. The present study would shed new light on the pathogenesis of cardiomyopathy and the cardioprotective mechanism of micronutrients.

Sequential Delivery and Cascade Targeting of Peptide Therapeutics for Triplexed Synergistic Therapy with Real-Time Monitoring Shuttled by Magnetic Gold Nanostars.

Due to the outstanding synergistic effects and low-toxicity, combination therapy exhibits more considerable potential in antitumor activity than monotherapy. Herein, a core-shell magnetic gold nanostar (Fe3O4@GNS, MGNS)-based system for codelivery of a mitochondrial targeting amphipathic tail-anchoring peptide (ATAP) and a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) was constructed. The magnetic core can facilitate delivery of the drug vehicle by external magnetic field, which results in accurate accumulation and enhances tumor cellular uptake for preliminary targeting. TRAIL and ATAP could sequentially target and be released toward the plasma membrane and mitochondria, initiating the extrinsic and intrinsic apoptosis pathways, respectively. The gold shell of MGNS can cause local tumor hyperthermia due to broad-band plasmon resonances in the near-infrared region, which can act as a complement with the peptide drug to further enhance apoptosis. Both in vitro and in vivo experiments revealed that rationally integrating extrinsic apoptosis, intrinsic apoptosis and hyperthermia for triplexed synergistic therapy, enabled the smart drug vehicle with pinpoint peptide drug delivery capabilities, and minimized side effects, enhancing the antitumor efficiency.

Taurine protected As2O3-induced the activation of hepatic stellate cells through inhibiting PPARα-autophagy pathway.

The activation of hepatic stellate cells (HSCs) is a key event in the development of hepatic fibrosis caused by arsenic. However, it is unclear how arsenic induces the activation of HSCs. In the present study, we found that arsenic trioxide (As2O3) induced liver tissue damage, stimulated autophagy and HSCs activation, and increased collagen accumulation in the liver of mice. Supplemented with taurine (Tau) attenuated the changes mentioned above caused by As2O3. In human hepatic stellate cell line LX-2 cells, we found that As2O3-induced activation of HSCs was autophagy-dependent, and we found that peroxisome proliferator activated receptors alpha (PPARα) played an important role in arsenic-induced HSCs activation. In addition, inhibiting autophagy and PPARα alleviated the activation of HSCs and lipid droplet loss induced by As2O3. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy and PPARα expression, and activation of the HSCs. Our results indicated that autophagy was regulated by PPARα and was involved in lipid droplet loss during the activation of HSCs. Tau alleviated As2O3-induced HSCs activation by inhibiting the PPARα/autophagy pathway. These findings give an innovative insight into the association of PPARα, autophagy, the activation of HSCs and hepatic fibrosis induced by As2O3.

Aptamer-Conjugated Au Nanocage/SiO2 Core-Shell Bifunctional Nanoprobes with High Stability and Biocompatibility for Cellular SERS Imaging and Near-Infrared Photothermal Therapy.

The combination of surface-enhanced Raman scattering (SERS) imaging technology with near-infrared (NIR) light-triggered photothermal therapy is of utmost importance to develop novel theranostic platforms. Herein, an aptamer-conjugated Au nanocage/SiO2 (AuNC/SiO2/Apt) core-shell Raman nanoprobe has been rationally designed as the bifunctional theranostic platform to fulfill this task. In this theranostic system, the Raman-labeled Au nanocage (AuNC) was encapsulated into a bioinert shell of SiO2, followed by conjugating aptamer AS1411 as the target-recognition moiety. AuNC served as the SERS-active and photothermal substrate due to its large free volume, built-in plasmon effect, and NIR photothermal capacity, while the SiO2 coating endowed the nanoprobes with good stability and biocompatibility, as well as abundant anchoring sites for surface functionalization. Considering their prominent SERS and photothermal properties, the application potential of the AuNC/SiO2/Apt nanoprobes was investigated. The proposed nanoprobes could be applied to targeted detection and SERS imaging of nucleolin-overexpressing cancer cells (MCF-7 cells as the model) from normal cells and also exhibited acceptable photothermal efficacy without systematic toxicity. This theranostic nanoplatform provided a possible opportunity for in situ diagnosis and noninvasive treatment of cancer cells by SERS imaging-guided photothermal therapy.

Inorganic arsenic induces pyroptosis and pancreatic ß cells dysfunction through stimulating the IRE1α/TNF-α pathway and protective effect of taurine.

Low-level inorganic arsenic (iAs) in drinking water is a risk factor for ß cells dysfunction. Taurine (Tau) is a kind of semi-essential ß amino acid, and beneficial for ß cell function. However, the effects of Tau on arsenic trioxide (As2O3) induced ß cells dysfunction and related mechanisms are still uncertain. Here, we found that Tau relieved As2O3-induced endoplasmic reticulum (ER) stress, inflammation and pyroptosis in rat pancreas. In INS-1 cells, with NOD-like receptor family pyrin domain-containing 3 (NLRP3) inhibitor pretreatment, As2O3-induced activation of pyroptosis was decreased; with tumor necrosis factor-α (TNF-α) inhibitor pretreatment, As2O3-induced activation of NLRP3 inflammasome and pyroptosis were decreased; further, with the inositol-requiring enzyme 1 alpha (IRE1α) inhibitor, As2O3-induced induction of TNF-α was decreased. Tau markedly protected As2O3-induced ß cells dysfunction by reducing the phosphorylation of IRE1α, production of TNF-α, activation of NLRP3 inflammasome and pyroptosis. Our results revealed that ER stress dependent inflammation and pyroptosis are critical pathogenic components of As2O3-induced ß cell dysfunction. Moreover, TNF-α was a critical signaling node that linked As2O3-induced ER stress and pyroptosis. Tau was an effective supplement against As2O3-induced ß cells dysfunction through the pathway as mentioned above.

Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway.

Arsenic exposure causes nonalcoholic steatohepatitis (NASH). Inflammation is a key contributor to the pathology of nonalcoholic fatty liver disease (NAFLD), including NASH. However, it is unclear how arsenic induces inflammation. In mouse livers, we show that arsenic trioxide (As2O3) induced NASH, increased autophagy and NLRP3 inflammasome activation, increased lipid accumulation, and resulted in dysregulation of lipid-related genes. Supplemented with taurine (Tau) attenuated the inflammation and autophagy caused by As2O3. In HepG2 cells, we found that As2O3-induced pyroptotic cell death was dependent upon the activation of NLRP3 inflammasome, which was CTSB-dependent. In addition, inhibiting autophagy alleviated the As2O3-induced increase of cytosolic CTSB expression and subsequent release of LDH, activation of the NLRP3 inflammasome, and pyroptosis. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy, CTSB expression, and activation of the NLRP3 inflammasome, and reduced the release of LDH, pyroptotic cell death, and inflammation. Interestingly, As2O3-induced lipid accumulation could not be alleviated by either inhibition of autophagy nor by inhibition of CTSB. Additionally, neither inhibition of the NLRP3 inflammasome or Tau treatment could alleviate lipid accumulation. These results demonstrated that As2O3-induced pyroptosis involves autophagy, CTSB, and the NLRP3 inflammasome cascade, and that Tau alleviates As2O3-induced liver inflammation by inhibiting the autophagic-CTSB-NLRP3 inflammasomal pathway rather than decreasing lipid accumulation. These findings give insight into the association of autophagy, inflammation, pyroptosis, and NASH induced by As2O3.

How Key Stakeholders Perceive a Smart Mobile Integrated Care System for the Elderly.

Integrated care has been an important model for caring the elderly. In China, it is still at its very early stage. We proposed a new model to develop a smart mobile system, taking the CARE instrument as the base and composed of apps for stakeholders. We did an usability study using the TAMM tool and, from a convenience sample of 11 elderly and 18 nurses, the results indicated the system was well appreciated.

Taurine Normalizes the Levels of Se, Cu, Fe in Mouse Liver and Kidney Exposed to Arsenic Subchronically.

To evaluate the benefits of taurine on the homeostasis of trace elements induced by toxic metals, we investigated the concentration of Selenium (Se), Copper (Cu), Iron (Fe) and Manganese (Mn) in mouse liver and kidney after arsenic exposure for 2 months. The experimental animals were divided into control group, arsenic exposure group (1, 2, 4 ppm) and taurine protective group randomly. Concentrations of serum, liver and kidney trace elements such as Se, Cu, Fe, Mn were measured by Inductively Coupled Plasma-Mass Spectrometry. Our results showed that the concentration of Cu was higher, however, the concentration of Se and Fe was lower in mice liver and kidney exposed to arsenic. The levels of Se, Cu, Fe were alleviated by co-administered with taurine. Furthermore, there was no difference in the concentration of Mn between the three groups. Our finding suggests that taurine may relieve the disturbed levels of Se, Cu and Fe in liver and kidney induced by arsenic.

Improvement of aquaponic performance through micro- and macro-nutrient addition.

Aquaponics is one of the "zero waste" industry in the twenty-first century, and is considered to be one of the major trends for the future development of agriculture. However, the low nitrogen utilization efficiency (NUE) restricted its widely application. To date, many attempts have been conducted to improve its NUE. In the present study, effect of micro- and macro-nutrient addition on performance of tilapia-pak choi aquaponics was investigated. Results showed that the addition of micro- and macro-nutrients improved the growth of plant directly and facilitated fish physiology indirectly, which subsequently increased NUE of aquaponics from 40.42 to 50.64%. In addition, remarkable lower total phosphorus concentration was obtained in aquaponics with micro- and macro-nutrient addition, which was attributed to the formation of struvite. Most of the added micro-nutrients were enriched in plant root, while macro-nutrients mainly existed in water. Moreover, no enrichment of micro- and macro-nutrients in aquaponic products (i.e., fish and plant leaves) was observed, indicating that it had no influence on food safety. The findings here reported manifest that appropriate addition of micro- and macro-nutrients to aquaponics is necessary, and would improve its economic feasibility.

Characteristic patterns of normal meridian acupoint temperature.

BACKGROUND: Body temperature is an important indicator of health and illness. However, a single temperature measurement is not always reliable. Such measurements can be made using meridians, which are energy channels with acupoints being the nodes. To date, there is no published reference of meridian acupoint temperatures applicable to human health, and there is no clear digitalized indicator that could be utilized to evaluate human health by way of meridian acupoints up to now. METHODS: Our study recruited 100 healthy medical college students for the measurement of acupoint temperature. The temperatures of 135 acupoints of 14 main meridians were measured using infrared thermometers in order to provide a comprehensive body temperature reading of each study participant. RESULTS: The degree of the acupoint temperature consistently ranged from 34.88°C to 36.14°C. The gross thermograph was concentric, with high degree readings around the heart and low degree readings originating from the feet. The left and right body sides had significant correlation between the degrees of bilateral same name acupoint temperatures of 12 regular meridians (correlation coefficient, 0.367-0.985; p < 0.0001). There was also a significant correlation between the acupoint temperature for the governor vessel and the conception vessel (correlation coefficient, 0.083; p = 0.006). CONCLUSION: These findings indicate that meridian acupoint temperature is characterized by a consistently narrow range, as well as concentricity and symmetry in body temperature degree readings in college students. Meridian acupoint temperature may be a sensitive and valuable indicator to assist in the accurate evaluation of meridian and general human health, and the significance and changes of acupoint temperature in clinical conditions warrants future exploration.

The role of oxidative stress in DNA damage in pancreatic ß cells induced by di-(2-ethylhexyl) phthalate.

Di(2-ethyhexyl) phthalate (DEHP) is commonly used as a plasticizer, which loosely binds to plastic materials and easily leaches out of these products and enters into the environment. Exposure to DEHP can impair pancreatic beta cells (INS-1 cells)function, which is associated with Insulin Resistance (IR) and type 2 diabetes. However, the mechanism of how DEHP leads to Insulin Resistance is unknown. Our results showed that the cell viability of INS-1 cells exposed to DEHP (0-1600 µM) were decreased in a concentration-dependent manner. DEHP caused significant increases of DNA migration and oxidative damage in INS-1 cells. Lysosomal membrane permeability was increased and mitochondrial membrane potential was reduced after INS-1 cells treated with DEHP. DEHP was also shown to induce ROS production and cause GSH depletion in INS-1 cells. DEHP brought a significant decrease in super oxide dismutase (SOD) and led to accumulation of malondialdehyde (MDA) in the INS-1 cells. DEHP increased significantly the expression of P53 and ATM gene of INS-1 cell at high dose levels. Simultaneously, Pyrroloquinoline Quinone (PQQ), an antioxidant, and alcohol were used in the study to determine their effects on DEHP-induced INS-1 cells damage. PQQ could protect the INS-1 cells from the damage induced by DEHP to some extent, while alcohol aggravated the toxic effects of DEHP. These results indicate that DEHP-mediated INS-1 cell dysfunction through a lysosomal-mitochondrial pathway, involving oxidative stress and p53 and ATM activation.