Chemical characteristics of long-term acid rain and its impact on lake water chemistry: A case study in Southwest China.

The chemical composition of acid rain and its impact on lake water chemistry in Chongqing, China, from 2000 to 2020 were studied in this study. The regional acid rain intensity is affected jointly by the acid gas emissions and the neutralization of alkaline substances. The pH of precipitation experienced three stages of fluctuating decline, continuous improvement, and a slight correction. Precipitation pH showed inflection points in 2010, mainly due to the total control actions of SO2 and NOx implemented in 2011. The total ion concentrations in rural areas and urban areas were 489.08 µeq/L and 618.57 µeq/L, respectively. The top four ions were SO42-, Ca2+, NH4+ and NO3-, which accounted for more than 90% of the total ion concentration, indicating the anthropogenic effects. Before 2010, SO42- fluctuated greatly while NO3- continued to rise; however, after 2010, both SO42- and NO3- began to decline rapidly, with the rates of -12.03 µeq/(L·year) and -4.11 µeq/(L·year). Because the decline rate of SO42- was 2.91 times that of NO3-, the regional acid rain has changed from sulfuric acid rain to mixed sulfuric and nitric acid rain. The lake water is weakly acidic, with an average pH of 5.86, and the acidification frequency is 30.00%. Acidification of lake water is jointly affected by acid deposition and acid neutralization capacity of lake water. Acid deposition has a profound impact on water acidification, and nitrogen (N) deposition, especially reduced N deposition, should be the focus of future research.

Sustainable, Insoluble, and Photonic Cellulose Nanocrystal Patches for Calcium Ion Sensing in Sweat.

Self-assembly of cellulose nanocrystals (CNCs) is invaluable for the development of sustainable optics and photonics. However, the functional failure of CNC-derived materials in humid or liquid environments inevitably impairs their development in biomedicine, membrane separation, environmental monitoring, and wearable devices. Here, a facile and robust method to fabricate insoluble hydrogels in a self-assembled CNC-polyvinyl alcohol (PVA) system is reported. Due to the reconstruction of inter- or intra-molecular hydrogen bond interactions, thermal dehydration makes an optimized CNC/PVA photonic film form a stable hydrogel network in an aqueous solution rather than dissolve. Notably, the resulting hydrogel exhibits superb mechanical performance (stress up to 3.3 Mpa and tough up to 0.73 MJ m-3 ) and reversible conversion between dry and wet states, enabling it convenient for specific functionalization. Sodium alginate (SA) can be adsorbed into the CNC photonic structure by swelling dry CNC/PVA film in a SA solution. The prepared hydrogel showcases the comprehensive properties of freezing resistance (-20°C), strong adhesion, satisfactory biocompatibility, and highly sensitive and selective Ca2+ sensing. The material could act as a portable wearable patch on the skin for the continuous analysis of calcium trends during different physical exercises, facilitating their development in precision nutrition and health monitoring.

Promoting heterotrophic denitrification of Pseudomonas hunanensis strain PAD-1 using pyrite: A mechanistic study.

Denitrification is critical for removing nitrate from wastewater, but it typically requires large amounts of organic carbon, which can lead to high operating costs and secondary environmental pollution. To address this issue, this study proposes a novel method to reduce the demand for organic carbon in denitrification. In this study, a new denitrifier, Pseudomonas hunanensis strain PAD-1, was obtained with properties for high efficiency nitrogen removal and trace N2O emission. It was also used to explore the feasibility of pyrite-enhanced denitrification to reduce organic carbon demand. The results showed that pyrite significantly improved the heterotrophic denitrification of strain PAD-1, and optimal addition amount was 0.8-1.6 g/L. The strengthening effect of pyrite was positively correlated with carbon to nitrogen ratio, and it could effectively reduce demand for organic carbon sources and enhance carbon metabolism of strain PAD-1. Meanwhile, the pyrite significantly up-regulated electron transport system activity (ETSA) of strain PAD-1 by 80%, nitrate reductase activity by 16%, Complex III activity by 28%, and napA expression by 5.21 times. Overall, the addition of pyrite presents a new avenue for reducing carbon source demand and improving the nitrate harmless rate in the nitrogen removal process.

The pathogenic characterization of Citrobacter freundii and its activation on immune related genes in Macrobrachium nipponense.

Out breaks of mass mortalities occurred in Macrobrachium nipponense farms in Jintan county, Jiangsu Province. The bacterial isolates from M. nipponense exhibited the same phenotypic traits and biochemical characteristics, and were identified as Citrobacter freundii according to biochemical characteristics and molecular identification. The infection test revealed that the strain YG2 was pathogenic to M. nipponense, and the half lethal dose (LD50) was 3.35 × 105 CFU/mL at 7 d post-infection. Detection of virulence genes indicated that YG2 was positive for cfa, ureG, ureF, ureE, ureD, viaB, ompX, and LDH. Furthermore, the results of extracellular enzyme analysis revealed that the strain can produce protease, amylase, lecithin, urease, and hemolysin. Antibiotic resistance results showed that the isolate was resistant to ampicillin, cefazolin, cephalothin, cefoxitin, aboren, doxycycline, neomycin, penicillin, erythromycin, and vancomycin. The expression level of MyD88, α2M, CDSP, and Relish were detected in hepatopancreas, hemolymph, gills and intestine tissues by quantitive real-time PCR (qRT-PCR), and clear transcriptional activation of these genes were observed in M. nipponense after C. freundii infection. These results revealed pathogenicity of C. freundii and its activation of host immune response, which will provide a scientific reference for the breeding and disease prevention in M. nipponense culture.

Metabolomic and Pathway Changes in Large-Leaf, Middle-Leaf and Small-Leaf Cultivars of Camellia sinensis (L.) Kuntze var. niaowangensis.

As an economically important crop, tea is widely cultivated in more than 50 countries and has numerous health benefits. Metabolomics has considerable advantages in the analysis of small molecules and has been widely used in tea science. We applied a metabolomic method to evaluate the dynamic changes in metabolites and pathways in the large-, middle- and small-leaf cultivars of Camellia sinensis (L.) Kuntze var. niaowangensis grown in the same area from Yunwu Mountain. The results indicate that flavonoid biosynthesis, stilbenoid, diarylheptanoid and gingerol biosynthesis, citrate cycle (TCA cycle), and propanoate metabolism may play important roles in the differences among cultivars. The levels of tea polyphenols, flavonoids and amino acids may impact the sensory properties of teas of different cultivars. Our results may help to elucidate the mechanism underlying the difference in tea quality and offer references for the breeding of high-quality tea cultivars.

ERK-dependent proteasome degradation of Txnip regulates thioredoxin oxidoreductase activity.

Dynamic control of thioredoxin (Trx) oxidoreductase activity is essential for balancing the need of cells to rapidly respond to oxidative/nitrosative stress and to temporally regulate thiol-based redox signaling. We have previously shown that cytokine stimulation of the respiratory epithelium induces a precipitous decline in cell S-nitrosothiol, which depends upon enhanced Trx activity and proteasome-mediated degradation of Txnip (thioredoxin-interacting protein). We now show that tumor necrosis factor-α-induced Txnip degradation in A549 respiratory epithelial cells is regulated by the extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinase pathway and that ERK inhibition augments both intracellular reactive oxygen species and S-nitrosothiol. ERK-dependent Txnip ubiquitination and proteasome degradation depended upon phosphorylation of a PXTP motif threonine (Thr349) located within the C-terminal α-arrestin domain and proximal to a previously characterized E3 ubiquitin ligase-binding site. Collectively, these findings demonstrate the ERK mitogen-activated protein kinase pathway to be integrally involved in regulating Trx oxidoreductase activity and that the regulation of Txnip lifetime via ERK-dependent phosphorylation is an important mediator of this effect.

Zbtb7b suppresses aseptic inflammation by regulating m6A modification of IL6 mRNA.

Radiotherapy is a crucial approach for treating tumors. However, radiation-induced aseptic inflammation is a common complication. Radiation pneumonitis is the acute manifestation of radiation-induced lung disease, and interleukin 6 (IL-6) is a major proinflammatory cytokine involved in radiation-induced lung injury. Here we found that silencing Zinc finger and BTB domain-containing protein 7B (Zbtb7b) resulted in higher radiation-induced IL-6 production in THP1 cells and BEAS-2B lung bronchial epithelial cells. Mechanistically, Zbtb7b recruited RNA demethylase ALKBH5 to IL6 mRNA. Subsequentially, it demethylated N6-methyladenosine (m6A) modification of IL6 mRNA and inhibited its nuclear export. Thus, Zbtb2b epigenetically suppresses irradiation-induced IL-6 production in the lungs via inhibiting the m6A modification and nucleocytoplasmic transport of IL6 mRNA, serving as a new potential predictive marker and therapeutic target in radiation pneumonitis treatment.

The migration direction of hair cell nuclei is closely related to the perinuclear actin filaments in Arabidopsis.

Nuclear migration in Arabidopsis root hairs is bidirectional and relies on actin filaments. However, how actin filaments regulate the bidirectional movement of nuclei remains unclear. Here, we discovered that nuclei migrate forward and backward according to the developmental stage of the hair cells. In addition, the migration direction of nuclei was not constant but reversed occasionally, accompanied by nuclear shape changes. Confocal microscopic analysis revealed that perinuclear actin bundles were closely related to the migration and shape of hair cell nuclei. Pharmacological studies showed that SMIFH2, an inhibitor of the actin nucleator-formin, inhibited nuclear backward migration probably by impairing the perinuclear actin filaments. These data indicate that nuclear migration in hair cells is likely motivated by the competition of mechanical forces acting on the nucleus. Furthermore, the perinuclear actin filaments are closely related to the migration direction of hair cell nuclei.

Curcumin protects against palmitic acid-induced apoptosis via the inhibition of endoplasmic reticulum stress in testicular Leydig cells.

BACKGROUND: Palmitic acid (PA) is a common saturated fatty acid that induces apoptosis in various types of cells, including testicular Leydig cells. There is evidence suggesting that PA is increased in patients with obesity and that PA-induced cell apoptosis may play an important role in obesity-related male infertility. Curcumin, a natural polyphenol, has been reported to exert cytoprotective effects in various cell types. However, the cytoprotective effect of curcumin against PA-induced apoptosis in Leydig cells remains unknown. Therefore, the current study was performed to investigate the protective effects of curcumin in response to PA-induced toxicity and apoptosis in murine Leydig tumor cell line 1 (MLTC-1) cells and explore the mechanism underlying its anti-apoptotic action. METHODS: MLTC-1 cells were cultured in Roswell Park Institute-1640 medium and divided into five groups. First four groups were treated with 50-400 µM PA, 400 µM PA + 5-40 µM curcumin, 400 µM PA + 500 nM 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), and 500 nM thapsigargin (TG, an ER stress inducer) + 20 µM curcumin, respectively, followed by incubation for 24 h. Effects of PA and/or curcumin on viability, apoptosis, and ER stress in MLTC-1 cells were then determined by cell proliferation assay, flow cytometry, and western blot analysis. The fifth group of MLTC-1 cells was exposed to 400 µM of PA and 5 IU/mL of human chorionic gonadotropin (hCG) for 24 h in the absence and presence of curcumin, followed by measurement of testosterone levels in cell-culture supernatants by enzyme-linked immunosorbent assay (ELISA). Rats fed a high-fat diet (HFD) were treated with or without curcumin for 4 weeks, and the testosterone levels were detected by ELISA. RESULTS: Exposure to 100-400 µM PA reduced cell viability, activated caspase 3, and enhanced the expression levels of the apoptosis-related protein BCL-2-associated X protein (BAX) and ER stress markers glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in MLTC-1 cells. Treating cells with 500 nM 4-PBA significantly attenuated PA-induced cytotoxicity through inhibition of ER stress. Curcumin (20 µM) significantly suppressed PA- or TG-induced decrease in cell viability, caspase 3 activity, and the expression levels of BAX, CHOP, and GRP78. In addition, treating MLTC-1 cells with 20 µM curcumin effectively restored testosterone levels, which were reduced in response to PA exposure. Similarly, curcumin treatment ameliorated the HFD-induced decrease in serum testosterone level in vivo. CONCLUSIONS: The present study suggests that PA induces apoptosis via ER stress and curcumin ameliorates PA-induced apoptosis by inhibiting ER stress in MLTC-1 cells. This study suggests the application of curcumin as a potential therapeutic agent for the treatment of obesity-related male infertility.

Spatiotemporal dynamics of cell abundance, colony size and intracellular toxin concentrations of pelagic and benthic Microcystis in Lake Caohai, China.

Lake Caohai has experienced extensive Microcystis blooms in recent years, and to improve its water quality, the local government carried out a series of water control measures. To better understand the dynamics of both pelagic and benthic Microcystis and their characteristics in Lake Caohai, we conducted a 1-year investigation from December 2015 to December 2016 to gain a seasonal outlook on the distribution and dynamics of cell abundance, colony size and intracellular microcystins (MCs) of Microcystis. The results indicated that the Microcystis bloom occupied primarily the northeastern region and then moved gradually from lakeshore to lake center. The perennial southwesterly winds and the water inflow from northeast to southwest in Lake Caohai determined the spatiotemporal distribution of pelagic Microcystis. Benthic Microcystis was mainly distributed in the northeastern region in summer, occupied the lake center in autumn and then occupied the southeastern region in winter, determined by the sedimentation of pelagic Microcystis and the death of benthic Microcystis. Small colonies (20-60 µm) overwintered more easily in both water column and sediment. The concentrations of intracellular toxin of benthic Microcystis were observed to be significantly higher than those of pelagic Microcystis. This might be because Microcystis synthesized large amount of MCs to acclimate to an unfavorable benthic environment. This knowledge on the dynamics of Microcystis expands our understanding of mechanisms underpinning the formation of Microcystis blooms.

The roles of bone morphogenetic protein 2 in perfluorooctanoic acid induced developmental cardiotoxicity and l-carnitine mediated protection.

Perfluorooctanoic acid (PFOA), a wide spread environmental pollutant, was associated with developmental cardiotoxicity in chicken embryo, while the underlying molecular mechanism had not been fully elucidated. In the current study, 2 mg/kg (egg weight) PFOA and/or 100 mg/kg (egg weight) l-carnitine were exposed to embryonic day zero (ED0) chicken embryo via air cell injection, and then bone morphogenic protein 2 (BMP2) silencing lentivirus or BMP2 recombinant protein were introduced into ED2 embryo. Electrocardiography and histological methods were utilized to assess the cardiac function and morphology in hatchling chickens, respectively. Consistent with previous results, 2 mg/kg PFOA exposure at ED0 significantly elevated heart rate and thinned right ventricular wall in hatchling chickens, while l-carnitine co-treatment reverted such changes. BMP2 silencing induced very similar changes in hatchling chicken hearts as PFOA exposure, while co-exposure of recombinant BMP2 protein alleviated PFOA-induced changes. l-carnitine exposure alleviated the BMP2-silencing induced changes as well. Western blotting revealed that PFOA exposure enhanced BMP2 expression and suppressed pSMAD1 expression in ED15 chicken embryo hearts, while both changes were reverted by l-carnitine co-exposure. Furthermore, silencing of BMP2 significantly increased the expression level of PPAR alpha in ED15 chicken embryo hearts, while silencing of PPAR alpha did not have significant impact on BMP2 expression. In conclusion, BMP2/pSMAD1 signaling participates in the PFOA-induced developmental cardiotoxicity in chicken embryo, which is likely located upstream of PPAR alpha for this particular endpoint. Protection of BMP2 signaling might contribute to l-carnitine mediated protection against PFOA-induced developmental cardiotoxicity.

Actin Bundles in The Pollen Tube.

The angiosperm pollen tube delivers two sperm cells into the embryo sac through a unique growth strategy, named tip growth, to accomplish fertilization. A great deal of experiments have demonstrated that actin bundles play a pivotal role in pollen tube tip growth. There are two distinct actin bundle populations in pollen tubes: the long, rather thick actin bundles in the shank and the short, highly dynamic bundles near the apex. With the development of imaging techniques over the last decade, great breakthroughs have been made in understanding the function of actin bundles in pollen tubes, especially short subapical actin bundles. Here, we tried to draw an overall picture of the architecture, functions and underlying regulation mechanism of actin bundles in plant pollen tubes.

The Roles of Reactive Oxygen Species and Nitric Oxide in Perfluorooctanoic Acid-Induced Developmental Cardiotoxicity and l-Carnitine Mediated Protection.

Perfluorooctanoic acid (PFOA) is an environmental contaminant that could induce developmental cardiotoxicity in a chicken embryo, which may be alleviated by l-carnitine. To explore the roles of reactive oxygen species (ROS) and nitric oxide (NO) in such changes and the potential effects of l-carnitine, fertile chicken eggs were exposed to PFOA via an air cell injection, with or without l-carnitine co-treatment. The ROS and NO levels in chicken embryo hearts were determined with electron spin resonance (ESR), and the protein levels of the nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) p65 and inducible nitric oxide synthase (iNOS) in chicken embryo hearts were assessed with western blotting. The results of ESR indicated that PFOA exposure induced an elevation in the ROS levels in ED19 chicken embryo hearts and hatchling chicken hearts, while l-carnitine could alleviate such changes. Meanwhile, increased NO levels were observed in ED19 embryo hearts and hatchling hearts following PFOA exposure, while l-carnitine co-treatment exerted modulatory effects. Western blotting revealed that p65 translocation in ED19 embryo hearts and hatchling hearts was enhanced by PFOA, while l-carnitine co-treatment alleviated such changes. iNOS expression levels in ED19 embryo hearts followed the same pattern as NO levels, while a suppression of expression was observed in hatchling hearts exposed to PFOA. ROS/NF-κB p65 and iNOS/NO seem to be involved in the late stage (ED19 and post hatch) of PFOA-induced developmental cardiotoxicity in a chicken embryo. l-carnitine could exert anti-oxidant and NO modulatory effects in the developing chicken embryo hearts, which likely contribute to its cardioprotective effects.

Synthesis and characterization of novel polyimides derived from 4,4'-bis(5-amino-2-pyridinoxy)benzophenone: effect of pyridine and ketone units in the main.

A diamine monomer, 4,4'-bis(5-amino-2-pyridinoxy)benzophenone, was designed and synthesized, and used to react with commercially different kinds of aromatic dianhydrides to prepare a series of polyimides containing pyridine and ketone units via the classical two-step procedure. Glass transition temperatures (Tg) of the resultant polyimides PI-(1-5) derived from 4,4'-bis(5-amino-2-pyridinoxy) benzophenone with various dianhydrides ranged from 201 to 310 °C measured by differential scanning calorimetry. The temperatures for 5%wt loss of the resultant polyimides in nitrogen atmosphere obtained from the thermogravimetric analysis curves fell in the range of 472-501 °C. The temperatures for 10%wt loss of the resultant polyimides in nitrogen atmosphere fell in the range of 491-537 °C. Meanwhile, the char yields at 800 °C were in the range of 55.3-60.8%. Moreover, the moisture absorption of polyimide films was measured in the range of 0.37-2.09%. The thin films showed outstanding mechanical properties with tensile strengths of 103-145 MPa, an elongation at break of 12.9-15.2%, and a tensile modulus of 1.20-1.88 Gpa, respectively. The coefficients of thermal expansion of the resultant polyimides were obtained among 26-62 ppm °C-1. To sum up, this series of polyimides had a good combination of properties applied for high-performance materials and showed promising potential applications in the fields of optoelectronic devices.

Highly optical transparency and thermally stable polyimides containing pyridine and phenyl pendant.

In order to obtain highly optical transparency polyimides, two novel aromatic diamine monomers containing pyridine and kinky structures, 1,1-bis[4-(5-amino-2-pyridinoxy)phenyl]diphenylmethane (BAPDBP) and 1,1-bis[4-(5-amino-2-pyridinoxy)phenyl]-1-phenylethane (BAPDAP), were designed and synthesized. Polyimides based on BAPDBP, BAPDAP, 2,2-bis[4-(5-amino-2-pyridinoxy)phenyl]propane (BAPDP) with various commercial dianhydrides were prepared for comparison and structure-property relationships study. The structures of the polyimides were characterized by Fourier transform infrared (FT-IR) spectrometer, wide-angle X-ray diffractograms (XRD) and elemental analysis. Film properties including solubility, optical transparency, water uptake, thermal and mechanical properties were also evaluated. The introduction of pyridine and kinky structure into the backbones that polyimides presented good optical properties with 91-97% transparent at 500 nm and a low cut-off wavelength at 353-398 nm. Moreover, phenyl pendant groups of the polyimides showed high glass transition temperatures (Tg ) in the range of 257-281 °C. These results suggest that the incorporating pyridine, kinky and bulky substituents to polymer backbone can improve the optical transparency effectively without sacrificing the thermal properties.

SIRT1/Atg5/autophagy are involved in the antiatherosclerosis effects of ursolic acid.

The purpose of this study was to investigate the antiatherosclerosis effects of ursolic acid (UA) in high-fat diet-fed quails (Coturnix coturnix) and potential mechanism. Quails were treated with high-fat diet (14 % pork oil, 1 % cholesterol w/w) with or without UA (50, 150, or 300 mg/kg/day) for 10 weeks. Serum lipid profile was assessed at 0, 4.5, and 10 weeks. After 10 weeks, serum antioxidant status and morphology of aorta were assessed. Additionally, human umbilical vein endothelial cells (HUVECs) were exposed to 100 µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 h, with or without pretreatment with UA (5, 10 or 20 µM) for 16 h, autophagy inhibitor 3-MA 5 mM for 2 h, or SIRT1 inhibitor EX-527 10 µM for 2 h. Cell viability and oxidative stress status were assessed and autophagy status was determined. Acetylation of lysine residue on Atg5 was assessed with immunoprecipitation. In results, high-fat diet negatively affected serum lipid profile and antioxidant status in quails and induced significant histological changes. Cotreatment with UA remarkably alleviated such changes. In HUVECs, ox-LDL treatment induced significant cytotoxicity along with oxidative stress, while UA cotreatment alleviated such changes significantly. UA treatment induced autophagy, enhanced SIRT1 expression, and decreased acetylation of lysine residue on Atg5. Cotreatment with 3-MA or EX-527 effectively abolished UA's protective effects. In summary, UA exerted antiatherosclerosis effects in quails and protected HUVECs from ox-LDL induced cytotoxicity, and the mechanism is associated with increased SIRT1 expression, decreased Atg5 acetylation on lysine residue, and increased autophagy.

Cytoprotective Effects of Oleanolic Acid in Human Umbilical Vascular Endothelial Cells is Mediated Via UCP2/ROS/Cytochrome C/AIF Pathway.

The aim of this study is to assess the potential protective effect of oleanolic acid (OA) against ox-LDL induced damage in human umbilical vascular endothelial cells (HUVECs) and investigate potential mechanism of action including antioxidative effects and inhibition of mitochondria apoptosis pathway. Cell counting kit 8 was used to evaluate the viability of HUVECs. 2', 7'-DCFH-DA staining and flow cytometry was used to assess the levels of intracellular reactive oxygen species in HUVECs. The protein expression levels of uncoupling protein 2, cytochrome C, and apoptosis induction factors were measured by western blotting. The results indicated that OA treatment alleviated ox-LDL induced cytotoxicity in HUVECs and ameliorated the reactive oxygen species levels. Western blotting results demonstrated that OA treatment increased the expression level of uncoupling protein 2 and decreased the release of cytochrome C and apoptosis induction factors from mitochondria to cytoplasm, suggesting inhibition of mitochondria apoptosis pathway. In conclusion, OA could protect HUVECs from ox-LDL-induced cytotoxicity; its antioxidant property and inhibition of mitochondria apoptosis are likely crucial contributors.

Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α.

Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment.

Physcion inhibits the metastatic potential of human colorectal cancer SW620 cells in vitro by suppressing the transcription factor SOX2.

AIM: Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro. METHODS: Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition (EMT) process and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA. RESULTS: Physcion (2.5, 5 mol/L) did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and invasion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of physcion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK3ß in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors. CONCLUSION: Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3ß signaling pathways and suppressing SOX2.

l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway.

In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l-carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway.