Comparative analysis of fecal microbiota composition diversity in Tibetan piglets suffering from diarrheagenic Escherichia coli (DEC).

This study was ascertained to investigate the adverse effects of pathogenic E. coli on gut microbiota of Tibetan piglets with history of yellow and white dysentery. For this purpose, a total of 18 fecal samples were collected from infected and healthy Tibetan piglets for 16S rRNA gene amplification and sequencing of V3-V4 region. Results showed that Firmicutes, Bacteroidia Fusobacteriota, Proteobacteria and Actinobacteriota were the predominant bacteria in Tibetan piglets at the level of phylum classification. Results on classification at family level showed that Lactobacillus, Bacteroidota, Fusobacteriota and Enterobacteriaceae were the dominant bacteria. Results on classification of bacteria at phylum level compared with normal piglets indicated that Bacteroidota, Actinobacteriota, Euryarchaota and Spirochaetota in fecal microbial community in Tibetan piglets showing yellow dysenteric and diarrhea group were significantly decreased (P ≤ 0.05). Compared with the feces of healthy Tibetan piglets, the abundance of Escherichia-Shigella, Lactobacillus and Enterococcus increased significantly in feces of Tibetan piglets having yellow dysentery and white dysentery. Moreover, results exhibited that the Proteobacteria and Fusobacteriota were significantly increased (P ≤ 0.05) suggesting dominant microbial community. Results revealed that E. coli induced different pathological alterations in intestine including damage to intestinal epithelial cells, infiltration of inflammatory cells, presence of red blood cells in spaces of tissues, hemorrhages and necrosis of intestinal villi in piglets with history of yellow dysentery. This study for the first time reported the composition, characteristics, and differences of the fecal microflora diversity of Tibetan piglets with yellow and white dysentery in Qinghai-Tibet Plateau, which can provide a suitable support for effective control of diarrhoeal disease in these animals.

Isolation, identification and biological characteristics of Mycoplasma bovis in yaks.

Mycoplasma bovis (M. bovis) is one of the important pathogens which may cause bovine respiratory disease syndrome (BRDS), and results in huge economic losses for yaks (Bos gaurus) breeding industry. However, there is limited information about M. bovis in yaks. In our study, 145 nasal mucus samples from yaks with pneumonia were collected to clarify. Bacteriological determination was carried out through biochemical identification and Polymerase Chain Reaction (PCR) detection. And ten strains of Mycoplasma bovis (M. bovis) were found from collected samples. Then, the growth curve of isolated strains was determined by the change of optical density (OD630), pH value and Color Change Cnit (CCU). K-B disk method was also used for antimicrobial susceptibility testing. Results of colony morphology and biochemical testing were consistent with the biological characters of M. bovis. The nucleotide sequences of uvrC specific gene and 16S rRNA gene among the 10 strains were highly homologous. The growth curve assay showed that the isolates cultured in PPLO medium were in lag phase for 24 h, entered stable period in 42 h, and entered decline phase after 78 h. The isolates were found resistant to macrolides, aminoglycosides and lincomycin at various degrees, but they were sensitive or moderately sensitive to doxycycline and kanamycin under antimicrobial susceptibility analysis. In conclusion, the results provided certain reference for the follow-up research and guiding for the treatment of M. bovis in yaks.

Calcium-Sensing Receptor Arbitrates Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells via the G Protein-PLC-IP3 Pathway.

Pulmonary arterial hypertension (PAH), also known as broilers ascites syndrome, is characterized by hypoxia, pulmonary artery pressure, and right heart failure. However, less information is available about the molecular mechanisms of PAH. We evaluated the mediation of calcium-sensing receptor by inducing hypoxia for the possible proliferation of pulmonary artery smooth muscle cells via the G protein pathway. For this purpose, we used an in vitro trial of chicken cell culture and confirmed our results by using immunohistochemistry, immunofluorescence staining, quantitative real-time polymerase chain reaction assay, and Western blotting analysis. Our results showed that the mRNA and protein expression levels of calcium-sensing receptor (CaSR) were significantly upregulated in cells when co-incubated with CaCl2. However, the levels of mRNA and protein were obviously decreased when supplemented with blocking agents (NiCl2, 2-APB, and D609). Furthermore, the experimentally induced hypoxia also upregulated the expression of CaSR gene as compared to CaSR gene expression in control cells. Together, these results indicate that hypoxia plays an important role in the expression of CaSR gene in pulmonary artery smooth muscle cells and reveals new targets for the CaSR excited hypothesis to prevent and control PAH in chickens.

MTA2 promotes HCC progression through repressing FRMD6, a key upstream component of hippo signaling pathway.

Discerning oncogenic drivers from passengers remains a major effort in understanding of the essence of the initiation and development of hepatocellular carcinoma (HCC), the most common primary liver malignancy and the third leading cause of cancer mortality worldwide. Here we report that MTA2, Metastasis Associated 1 Family Member 2, is significantly up-regulated in HCC. We show that high level of MTA2 expression is strongly correlated with advanced pathological stages and poor overall survival of the patients. Genome-wide identification of the transcriptional targets of MTA2 by ChIP-seq indicates that MTA2 represses a cohort of genes including FRMD6 that are critically involved in the growth and mobility of HCC. We demonstrate that the MTA2 promotes the proliferation and metastasis of HCC in vitro and in vivo through suppressing Hippo signaling pathway. Together, these results reveal a key role for the MTA2-FRDM6-Hippo axis in human hepatocarcinogenesis.

Seroprevalence and risk factors associated with Pseudorabies virus infection in Tibetan pigs in Tibet.

BACKGROUND: Pseudorabies (PR) is an important emerging infectious disease that is characterized by fever, extreme itching and encephalomyelitis. However, it is still unclear whether Tibetan pigs are exposed to Pseudorabies virus (PRV) or not. The present study was conducted to investigate the seroprevalence of PRV infection in Tibetan pigs in Nyingchi area of Tibet through enzyme-linked immunosorbent assay (ELISA). A total of 368 serum samples from Tibetan pigs were collected during 2015. RESULTS: Results showed that 58 (15.76%) samples were found positive for PRV antibodies with further distribution of 18.23%, 13.42% and 6.25% from Nyingchi, Mainling and Gongbo'gyamda areas on the Tibetan plateau, respectively; along with 12.10%, 17.71% and 17.57% prevalence of PRV in juveniles, sub-adults and adults, respectively. The prevalence of PRV infection between male (14.61%) and female (16.84%) showed non-significant difference (P > 0.05). The risk factors of infection were found to be associated with feed type, age and altitude. CONCLUSIONS: The present study depicts a serious concern with a new emerging infectious disease in Tibetan pigs in Tibet, China.

First report of Ehrlichia infection in goats, China.

Ehrlichiosis is an emerging infectious disease of domestic animals which is transmitted by ticks. This disease has been reported earlier in most parts of China in dogs, cattle and humans, but there is no published data regarding this disease in goats. The present study provided the evidence of Ehrlichia infection in goats in Wuhan, China on the basis of clinical signs, gross lesions, serum-biochemical, histopathological and PCR. Twenty four goats were presented to the veterinary hospital of Huazhong Agricultural University during July, 2016. The goats were diagnosed for Ehrlichia in monocytic and granulocytic forms by blood smear examination. Further confirmation was done by PCR examination, while histopathological examination revealed degeneration and inflammation in different tissues. The biochemical criterion and blood samples analysis showed significant (P < 0.05) changes. The present study reported that goats are naturally exposed to Ehrlichia infection. To the best of our knowledge, this is the first clinical report of Ehrlichia infection in goats infested with infected ticks.

Relationship between pathogenic E.coli O78-induced intestinal epithelial barrier damage and Zonulin expression levels in yaks.

To explore whether the intestinal damage of yak colibacillosis resulted from the regulation of Zonulin expression by its pathogenic bacteria, the overexpression and interference plasmids of Zonulin were designed and cultured in Tranwell after cell transfection. Then qRT-PCR and Western blot were used to detect the results of cell transfection, 200 mL 1×105 CFU/mL E.coli O78 was added for 4 hours, transmembrane resistance was measured by transmembrane resistance meter, FD4 fluorescence concentration in the lower chamber was detected by enzyme labeling instrument, bacterial translocation was measured by CFU counting method, and epithelial mucin (MUC1, MUC2) and tight junction protein (FABP2, Occludin, ZO-1) were detected by qRT-PCR. Results: The Zonulin gene overexpression and knockout cell lines were successfully constructed, the TEER value of the barrier of Zonulin overexpression cell lines began to decrease at 1 h after the addition of E.coli O78 and reached the lowest value at 4 h, and the TEER value of Zonulin interference cell lines decreased within 1-4 h after the addition of E.coli O78. At 4 h, the FD4 passing capacity of Zonulin overexpression cell lines was significantly higher than that of interfering cell lines, reaching twice as much as siRNA-1. The amount of bacterial translocation in overexpressed cell lines increased rapidly within 1-4 h, and the concentration of E.coli in the lower chamber was significantly higher than that in the siRNA-1 group at 4 h, but there was no significant change in the siRNA-1 group in the 1-4 h. There was no significant change in the mRNA level of MUC1 in Zonulin overexpression and interference cell lines after the addition of E.coli O78. In the overexpression group, the mRNA levels of MUC2, Occludin, and ZO-1 were significantly decreased, and the mRNA level of FABP2 was increased considerably. These results suggest stimulate epithelial cells to secrete Zonulin protein. Many Zonulin proteins regulate the opening of tight junction structures, reduce the transmembrane resistance of the cell barrier, and improve the permeability of the cell barrier and the amount of bacterial translocation.

The Resistance Mechanism of Mycoplasma bovis From Yaks in Tibet to Fluoroquinolones and Aminoglycosides.

Mycoplasma bovis (M. bovis) is one of the important pathogens for yaks. Aminoglycosides and fluoroquinolones are frequently used medications for the treatment of M. bovis. Drug-resistant strains were inevitable with the abuse of antibiotics. The resistance of M. bovis to aminoglycosides was related to the base mutations in drug target genes. Amino acid mutations at the quinolone resistance-determining region (QRDR) in gyrA, gyrB, parC, and parE conferred resistance to fluoroquinolones. In order to investigate the resistance mechanism of M. bovis from yaks in Tibet to aminoglycosides and fluoroquinolones, six frequently used antibiotics and ten clinical M. bovis strains were administered for a drug sensitivity test for in vitro-induced highly resistant strains, a drug stable-resistance test, cross-resistance test, and analysis of target gene mutations. The results showed that the clinical strains of M. bovis from yaks in Tibet had varying degrees of resistance to fluoroquinolones and aminoglycosides. The mechanism of resistance to fluoroquinolones and aminoglycosides was identified preliminarily for M. bovis from yaks: the single-site base mutation mediated the resistance of M. bovis from yaks and both base mutations led to highly resistant strains (aminoglycosides: rrs3 and rrs4; fluoroquinolones: gyrA and parC). The active efflux system results of M. bovis showed that there was no active efflux system based on fluoroquinolones and aminoglycosides expressed in M. bovis from yaks. The research could provide a reference for clinical treatment of M. bovis.

Seroprevalence and Risk Factors Investigations of Parvovirus Disease in Tibetan Pigs: First Report from Tibet.

Porcine parvovirus (PPV) disease is a worldwide spread animal disease with high infection rate and serious impact on meat economy causing significant losses in livestock production. The purpose of this paper is to investigate and analyze the regional seroprevalence of PPV in Tibetan pigs in Tibet and evaluate risk factors related to the disease. A total of 356 serum samples of Tibetan pigs were collected from four counties and districts in Tibet, and anti-PPV antibodies were detected by using a commercial competitive ELISA. Our results show a seroprevalence of 91.01% (324 serum samples were found to be positive for anti-PPV antibodies). The positive rate among different district was 100%, 96.55%, 93.68% and 72.83%, respectively in the Mainling County, in Bayi district, Nang County and Bomê County. We found significant differences between different age and gender groups; particularly female animals show a seroprevalence of 96.03% while the males only 83.46%. From the perspective of the growth stage, our results indicate that subadults show a seroprevalence significative higher than other age groups (100%). This study describes for the first time the PPV seroprevalence among Tibetan pigs characterizing risk factors involved in its transmission and providing information to be taken into account for eventual surveillance or eradication plans.

Remodeling of the microbiota improves the environmental adaptability and disease resistance in Tibetan pigs.

Introduction: The establishment of intestinal microbiota and the maintenance of its equilibrium structure plays an important role in Tibetan pigs during different growth stages. Understanding the structure and function of the intestinal microbiota at different growth stages of Tibetan pigs can provide a theoretical basis for guiding nutritional regulation and feeding management in different stages. Methods: Fecal samples were collected from the Tibetan piglets at different growth stages, and the 16S rRNA was sequenced to analyze the changes of intestinal microbiota. Results: Alpha and Beta diversity indexes showed that the diversity of the intestinal microbiota did not change during the three growth stages, and the main components of intestinal microbiota were not significantly different. At the phylum level, Firmicutes and Bacteroidetes were dominant and abundant at different growth stages and were not restricted by age. At the genus level, Streptococcus, Lactobacillus, and Bifidobacterium were the most dominant in the TP10d and TP40d groups, Streptococcus was the most dominant in the TP100d group, followed by Treponema_2 and Lactobacillus. Fusobacteria, Gluconobacter, and Synergistetes were found to be specific genera of 10-day-old Tibetan piglets by LEfSe combined with LDA score. The change of diet made Tenericutes and Epsilonbacteraeota, which are closely related to digestive fiber, become specific bacteria at the age of 40 days. With the consumption of oxygen in the intestine, obligate anaerobes, such as Verrucomicrobia, Fibrobacter, and Planctomycetes, were the characteristic genera of 100 days. KEGG function prediction analysis showed that the intestinal microbiota function of Tibetan pigs changed dynamically with the growth and development of Tibetan piglets. Discussion: In conclusion, the structure and composition of the intestinal microbiota of Tibetan pigs are significantly different at different growth and development stages, which plays an important role in their immune performance.

Synergy of Losartan and chemotherapy for patients with cholangiocarcinoma: A propensity score-matched analysis.

Background: Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelial cells that no obvious clinical symptoms and specific clinical manifestations are shown in the early stage of CCA. Methods: Propensity score matching (PSM) is a quasi-experimental method in which this study used. Patients were enrolled from Department of General surgery, First Affiliated Hospital of Jinzhou Medical University from March 1, 2010, to December 30, 2019. Totally 170 patients with CCA were enrolled in this study. Results: We performed a 1:2 PSM study and found that patients with losartan group showed both comparable median OS (overall survival) and TTR (time to recurrence) to those in the patients without losartan group before PSM. However, after matching, patients with losartan group showed favorable median OS and TTR than those in the patients without losartan group. Then we performed Cox proportional hazards models and found that patients with losartan was an independent factor after multivariable analysis for patients with CCA. Furtherly, we sequenced serial cfDNA were performed in 10 patients with losartan and 9 patients without losartan who received adjuvant chemotherapy after tumor resection. These results showed that the treatment of losartan was related with tumor microenvironment and could be potentially useful to combine the immunotherapy for patients with CCA. Conclusion: In conclusion, this study demonstrated that the treatment of losartan could increase the efficacy of adjuvant chemotherapy and identified as an independent survival predictor for patients with CCA. Moreover, losartan could be potentially useful to combine the immunotherapy for patients with CCA.

ZNF774 is a potent suppressor of hepatocarcinogenesis through dampening the NOTCH2 signaling.

Discerning oncogenic drivers from passengers remain a major effort in understanding of the essence of the initiation and development of hepatocellular carcinoma (HCC), which is the most common primary liver malignancy and the third leading cause of cancer mortality worldwide. Here we report that ZNF774, a novel zinc-finger protein, inhibits the proliferation and invasion of HCC cells. Molecular characterization of this protein indicated that ZNF774 acts as a transcription repressor, and interrogation of ZNF774 interactome by affinity purification-coupled mass spectrometry revealed that ZNF774 is physically associated with the Mi-2/nucleosome remodeling and deacetylase (NuRD) complex in cells. Genome-wide identification of the transcriptional targets of the ZNF774/NuRD complex by ChIP-seq indicated that ZNF774 represses a cohort of genes including NOTCH2 that are critically involved in the growth and mobility of HCC. We demonstrated that the ZNF774/NuRD complex inhibits the proliferation and invasion of HCC cells in vitro and suppresses HCC growth and metastasis in vivo. Importantly, the expression of ZNF774 is significantly downregulated in HCC, and low ZNF774 expression strongly correlated with high NOTCH2 expression, advanced pathological stages, and poor overall survival of the patients. Together, these results uncover a key role for the ZNF774/NuRD-NOTCH2 axis in hepatocarcinogenesis.

Increase in cases of dengue in China, 2004-2016: A retrospective observational study.

BACKGROUND: Dengue fever (DF) is a vector-bore infectious disease that can infect humans, and has been recognized as a global public health threat, with significant morbidity and mortality rates. METHOD: To describe the epidemiological profile of DF in China during 2004-2016, the morbidity data of DF by age-group, season (different months) and geographic location (different provinces) were obtained from the public health science data center of China for subsequent epidemiological analysis. RESULTS: The results showed that the incidence of DF shows striking annual variations, and two large outbreaks occurred in 2006-2007 and during 2012-2015. The results of the average morbidity rates (cases/100,000 population) for human DF indicated that among all dengue fever cases, Guangdong in southern area of China had the highest rates (3.8160 cases/100,000 population), followed by Yunnan (0.6614 cases/100,000 population), Fujian (0.3463 cases/100,000 population) and Guangxi (0.1474 cases/100,000 population). Epidemic peaks occurred in late June and early November, and the incidence rate among middle-aged people (30-45 years old) was relatively high, followed by rates among 15-29 and 45-59 age groups. CONCLUSION: In this study, we demonstrated the epidemiological profile of DF circulating in China and revealed the geographic distribution, dynamic transmission, seasonal asymmetries and age distribution, which will provide guidelines on the prevention and control of DF in China. The present investigation is useful in the risk assessment of DF transmission, to predict DF outbreaks and the prevention and control strategies should be used along with surveillance to reduce the spread of DF in China.

Exosome-derived uterine miR-218 isolated from cows with endometritis regulates the release of cytokines and chemokines.

As an inflammation of the endometrium, endometritis can affect fertility and lead to serious economic losses in the dairy industry. Widely found in various tissues and body fluids, exosomes and exosome micro (mi)RNAs have been shown to play an important regulatory role in the immune responses. As one of differentially expressed exosome miRNAs, miR-218 is involved in the pathogenesis of bovine endometritis. The mechanisms of miR-218 in regulating the release of cytokines and chemokines in endometritis, however, are poorly understood. Exosomes were isolated from bovine uterine cavity fluid and verified by transmission electron microscopy. An in vitro lipopolysaccharide-treated cell model for bovine endometritis was then established to evaluate the correlation between exosome-derived miR-218 and the immune responses. We demonstrated that exosomes could be used to deliver miR-218 from endometrial epithelial cells (EECs) into the uterine microenvironment and adjacent recipient cells to modulate local immune responses. miR-218 packaged in the exosomes secreted from EECs acts as an inhibitor by blocking immune factors such as interleukin (IL)-6, IL-1ß, tumour necrosis factor-α, the chemokines macrophage inflammatory genes (MIP)-1α and MIP-1ß to maintain the immune balance in the uterus. However, uterine inflammation altered the immunoregulatory mechanism of exosome miR-218. MiR-218 is a potential biomarker for the detection of endometritis. Our findings also revealed a new mechanism for the development of endometritis in cows.

Correction: ZNF774 is a potent suppressor of hepatocarcinogenesis through dampening the NOTCH2 signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Snail promotes the generation of vascular endothelium by breast cancer cells.

A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial-mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.

Therapeutic Progress and Knowledge Basis on the Natriuretic Peptide System in Heart Failure.

Notwithstanding substantial improvements in diagnosis and treatment, Heart Failure (HF) remains a major disease burden with high prevalence and poor outcomes worldwide. Natriuretic Peptides (NPs) modulate whole cardiovascular system and exhibit multiple cardio-protective effects, including the counteraction of the Renin-Angiotensin-Aldosterone System (RAAS) and Sympathetic Nervous System (SNS), promotion of vasodilatation and natriuresis, and inhibition of hypertrophy and fibrosis. Novel pharmacological therapies based on NPs may achieve a valuable shift in managing patients with HF from inhibiting RAAS and SNS to a reversal of neurohormonal imbalance. Enhancing NP bioavailability through exogenous NP administration and inhibiting Neutral Endopeptidase (NEP) denotes valuable therapeutic strategies for HF. On the one hand, NEP-resistant NPs may be more specific as therapeutic choices in patients with HF. On the other hand, NEP Inhibitors (NEPIs) combined with RAAS inhibitors have proved to exert beneficial effects and reduce adverse events in patients with HF. Highly effective and potentially safe Angiotensin Receptor Blocker Neprilysin Inhibitors (ARNIs) have been developed after the failure of NEPIs and Vasopeptidase Inhibitors (VPIs) due to lacking efficacy and safety. Therapeutic progress and knowledge basis on the NP system in HF are summarized in the current review.

GATA1 Promotes Gemcitabine Resistance in Pancreatic Cancer through Antiapoptotic Pathway.

Gemcitabine-based chemotherapy is the first-line treatment for pancreatic cancer. However, chemoresistance is a major obstacle to drug efficacy, leading to poor prognosis. Little progress has been achieved although multiple mechanisms are investigated. Therefore, effective strategies are urgently needed to overcome drug resistance. Here, we demonstrate that the transcription factor GATA binding protein 1 (GATA1) promotes gemcitabine resistance in pancreatic cancer through antiapoptotic pathway. GATA1 is highly expressed in pancreatic ductal adenocarcinoma (PDAC) tissues, and GATA1 status is an independent predictor of prognosis and response to gemcitabine therapy. Further investigation demonstrates GATA1 is involved in both intrinsic and acquired gemcitabine resistance in PDAC cells. Mechanistically, we find that GATA1 upregulates Bcl-XL expression by binding to its promoter and thus induces gemcitabine resistance through enhancing Bcl-XL mediated antiapoptosis in vitro and in vivo. Moreover, in PDAC patients, Bcl-XL expression is positively correlated with GATA1 level and predicts clinical outcomes and gemcitabine response. Taken together, our results indicate that GATA1 is a novel marker and potential target for pancreatic cancer. Targeting GATA1 combined with Bcl-XL may be a promising strategy to enhance gemcitabine response.

Transcriptome analysis reveals the molecular mechanism of hepatic metabolism disorder caused by chromium poisoning in chickens.

Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxicity, while the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is unclear. We demonstrated the induction of chromium poisoning model in chickens to identify the differentially expressed genes (DEGs), and their functions were analyzed under different physiological and pathological conditions. Histopathological examination and transcriptome data for chromium-poisoned livers and control livers were annotated with Illumina® HiSeq 2000. The histopathological examination in chromium poisoning groups showed diapedesis, hemolysis, degeneration, nucleus pycnosis, and central phlebectasia in the liver. A total of 334 genes were upregulated and 509 genes were downregulated. The most strongly upregulated genes were HKDC1, DDX4, ACACA, FDFT1, CYYR1, PPP1R3C, and SLC16A14, while the most downregulated genes were MYBPC3, CCKAR, PCK1, and CPT1A. A Gene Ontology (GO) term with the highest enrichment of DEGs is small molecule metabolic process. In cell component domain, the term with the highest enrichment is extracellular matrix. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that glucose metabolism, lipid metabolism, and protein metabolism were the most important metabolic pathways in the liver. The current study first time provides important clues and evidence for identifying the differentially expressed genes in livers due to Cr (VI)-induced liver injury in chickens.

Nano Copper Induces Apoptosis in PK-15 Cells via a Mitochondria-Mediated Pathway.

Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40-100 µg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 µg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 µg/mL. To summarize, nano copper significantly (P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.