From pill to pain: Alendronate-induced esophageal injury-A case report and review.

Background: Alendronate is used to treat Paget's bone disease, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop bone resorption. Case report: We present an exceptional case of esophagitis caused by alendronate. Blood tests and other data were normal when the patient was taken to the hospital, but an endoscopic examination revealed significant esophageal redness, erosion, and ulceration, along with pseudomembrane. The patient was given medicine after receiving a diagnosis of alendronate pill-induced esophagitis based on the pathological findings. Conclusion: This case report is a timely reminder of the importance of thorough pharmacovigilance, patient education, and smart therapeutic decision-making in the context of alendronate use. To properly treat and prevent problems with the esophagus caused by alendronate, additional research is required.

Lead induced cerebellar toxicology of developmental Japanese quail (Coturnix japonica) via oxidative stress-based Nrf2/Keap1 pathway inhibition and glutathione-mediated apoptosis signaling activation.

Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to birds still needs further study. In this study, we examined the neurotoxic effects of Pb exposure on avian cerebellum by using an animal model-Japanese quail (Coturnix japonica). The one-week old male chicks were exposed to 50, 200 and 500 mg/kg Pb of environmental relevance in the feed for five weeks. The results showed Pb caused cerebellar microstructural damages charactered by deformation of neuroglia cells, granule cells and Purkinje cells with Nissl body changes. Moreover, cerebellar neurotransmission was disturbed by Pb with increasing acetylcholine (ACh) and decreasing acetylcholinesterase (AChE), dopamine (DA), γ-Aminobutyric Acid (GABA) and Na+/K+ ATPase. Meanwhile, cerebellar oxidative stress was caused by Pb exposure represented by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) as well as decreasing catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH) and superoxide dismutase (SOD). Moreover, RNA-Seq analysis showed that molecular signaling pathways in the cerebellum were disrupted by Pb exposure. In particular, the disruption of nuclear factor erythroid-2-related factor 2 (Nfr2)/kelch-like ECH-associated protein 1 (Keap1) pathway and glutathione metabolism pathway indicated increasing cell apoptosis and functional disorder in the cerebellum. The present study revealed that Pb induced cerebellar toxicology through structural injury, oxidative stress, neurotransmission interference and abnormal apoptosis.

Polystyrene microplastics disrupted physical barriers, microbiota composition and immune responses in the cecum of developmental Japanese quails.

Microplastics, a new type of emerging pollutant, is ubiquitous in terrestrial and water environments. Microplastics have become a growing concern due to their impacts on the environment, animal, and human health. Birds also suffer from microplastics contamination. In this study, we examined the toxic effects of polystyrene microplastics (PS-MPs) exposure on physical barrier, microbial community, and immune function in the cecum of a model bird species-Japanese quail (Coturnix japonica). The one-week-old birds were fed on environmentally relevant concentrations of 20 µg/kg, 400 µg/kg, and 8 mg/kg PS-MPs in the diet for 5 weeks. The results showed that microplastics could cause microstructural damages characterized by lamina propria damage and epithelial cell vacuolation and ultrastructural injuries including microvilli breakage and disarrangement as well as mitochondrial vacuolation in the cecum of quails. In particular, blurry tight junctions, wider desmosomes spacing, and gene expression alteration indicated cecal tight junction malfunction. Moreover, mucous layer breakdown and mucin decrease indicated that chemical barrier was disturbed by PS-MPs. PS-MPs also changed cecal microbial diversity. In addition, structural deformation of cecal tonsils and increasing proinflammatory cytokines suggested cecal immune disorder and inflammation responses by PS-MPs exposure. Our results suggested that microplastics negatively affected digestive system and might pose great health risks to terrestrial birds.

Microplastics induced inflammation in the spleen of developmental Japanese quail (Coturnix japonica) via ROS-mediated p38 MAPK and TNF signaling pathway activation1.

Microplastics (MPs) have been found in virtually every environment on earth and become a source of pollution around the world. The toxicology of microplastics on immunity is an emerging area of research, and more studies are needed to fully understand the effects of microplastics exposure on animal health. Therefore, we tried to determine the immunotoxic effects of microplastics on avian spleen by using an animal model- Japanese quail (Coturnix japonica). One-week chicks were exposed to environmentally relevant concentrations of 0.02 mg/kg, 0.4 mg/kg and 8 mg/kg polystyrene microplastics in the feed for 5 weeks. The results demonstrated that microplastics induced microstructural injuries featured by cell disarrangement and vacuolation indicating splenic inflammation. Ultrastructural damages including membrane lysis and mitochondrial vacuolation also suggested inflammatory responses in the spleen by microplastics exposure. Meanwhile, increasing reactive oxygen species (ROS) and Malondialdehyde (MDA) while the inactivation of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) indicated oxidative stress in the spleen. Moreover, the increasing level of proinflammatory cytokines including Tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and decreasing level of anti-inflammatory cytokine interleukin-10 (IL-10) implied splenic inflammation. Furthermore, transcriptomic analysis showed that microplastics induced inflammatory responses in the spleen through p38 mitogen-activated protein kinases (p38 MAPK) pathway activation and tumor necrosis factor (TNF) signaling stimulation. The signaling stimulation also aggravated cell apoptosis in the spleen. The present study may benefit to understand potential mechanisms of developmental immunotoxicology of microplastics.

Lead exposure disrupted ileal barrier of developmental Japanese quails(Coturnix japonica): Histopathological damages, microbiota dysbiosis and immune disorder.

The gut barrier plays an essential role in maintaining homeostasis and is usually composed of a mechanical barrier, a chemical barrier, an immune barrier, and a biological barrier. However, the impacts of lead (Pb) exposure on avian gut barrier are still unclear. Therefore, the present study tried to determine the toxic effects of Pb on ileal barrier of a biological model-Japanese quail (Coturnix japonica). One-week old quails were exposed to 0, 50, 500 and 1000 ppm Pb in drinking water for 5 weeks. The results showed mechanic barrier in the ileum was disrupted with microstructural deformation featured by epithelial cell abscission, villi contractions and goblet cells reduction as well as ultrastructural changes characterized by swollen mitochondria, blurry tight junctions and microvilli subtraction. Meanwhile, the expression of genes associated with intestinal tight junctions was downregulated in Pb-treated groups indicating tight junction malfunction. Moreover, less mucus and downregulation of expression of mucin2 (Muc2) and Krüppel-like factor 4 (Klf4) indicated chemical barrier disturbance by Pb. In addition, the alteration of microbial diversity and emergence of pathogen bacteria suggested ileal biological barrier disruption by Pb. Furthermore, Pb caused immune dysfunction in the ileum through promoting the expression of pro-inflammatory factors including interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), Interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NF-κB) and inhibiting the expression of anti-inflammatory factor interleukin 10 (IL-10). The present study demonstrated that Pb may pose health risks to birds through gut barrier damages.

Tracking the Progression of the Simulated Bronze Disease-A Laboratory X-ray Microtomography Study.

The internal three-dimensional characteristics of X-ray microtomography (micro-CT) has great application potential in the field of bronze corrosion. This work presents a method of simulating bronze disease based on an in situ micro-CT image to study the characteristics of the oxidative hydrolysis reactions of copper(I) chloride and copper(II) chloride dihydrate. A series of high-resolution reconstruction images were obtained by carrying out micro-CT at three key points throughout the experiment. We found that the reactions of copper(I) chloride and copper(II) chloride dihydrate showed different characteristics at different stages of the simulation in the micro-CT view. The method proposed in this work specifically simulated one single type of bronze corrosion and characterized the evolution characteristics of simulated bronze disease. It provides a new perspective to investigate bronze disease and can help improve the subsequent use of micro-CT to distinguish real bronze corrosions.

Lead exposure induced developmental nephrotoxicity in Japanese quail (Coturnix japonica) via oxidative stress-based PI3K/AKT pathway inhibition and NF-κB pathway activation.

Birds are sensitive to environmental pollution and lead (Pb) contamination could negatively affect nearly all avian organs and systems including kidney of excretive system. Thereby, we used a biological model species-Japanese quail (Coturnix japonica) to examine the nephrotoxic effects of Pb exposure and possible toxic mechanism of Pb on birds. Quail chicks of 7-day-old were exposed to 50 ppm Pb of low dose and high dose of 500 ppm and 1000 ppm Pb in drinking water for five weeks. The results showed that Pb exposure induced kidney weight increase while body weight and length reduction. The increase of uric acid (UA), creatinine (CREA) and cystatin c (Cys C) in the plasma suggested renal dysfunction. Moreover, both microstructural and ultrastructural changes demonstrated obvious kidney damages. In particular, renal tubule epithelial cells and glomeruli swelling indicated renal inflammation. Furthermore, changes in the content and activity of oxidative stress markers suggested that Pb caused excessive oxidative stress in the kidney. Pb exposure also induced abnormal apoptosis in the kidney. In addition, RNA sequencing (RNA-Seq) analysis revealed that Pb disturbed molecular pathways and signaling related with renal function. Especially, Pb exposure resulted in an increase in renal uric acid synthesis by disrupting purine metabolism. Pb caused apoptotic increment by inhibiting the phosphatidylinositol-3-kinase (PI3K)/RAC-alpha serine/threonine-protein kinase (AKT) pathway and induced aggravated inflammation by activating Nuclear Factor kappa B (NF-κB) signaling pathway. The study implied that Pb caused nephrotoxicity through structural damages, uric acid metabolism disorder, oxidation imbalance, apoptosis and inflammatory pathway activation.

Facile, Controllable, and Ultrathin NiFe-LDH In Situ Grown on a Ni Foam by Ultrasonic Self-Etching for Highly Efficient Urine Conversion.

As the primary source of nitrogen pollutants in domestic sewage, urine is also an alternative for H2 production via electrochemical processes. However, it suffers from sluggish kinetics and noble-metal catalyst requirement. Here, we report a non-precious ultrathin NiFe-layered double hydroxide catalyst for the remarkable conversion of urea into N2 and H2, which is in situ grown on a Ni foam via ultrasonic self-etching in Fe3+/ethylene glycol (EG). EG regulates the etching rate of Fe3+, resulting in an ultrathin nanosheet structure with the aid of ultrasonication. This structure dramatically promotes the dehydrogenation process via decreasing the nanolayer thickness from 120 to 3.4 nm and leads to a 4.8-fold increase in the generation of active sites. It exhibits record urea oxidation kinetics (390.8 mA·cm-2 at 1.5 V vs RHE) with excellent stability (120 h), which is 11.8 times better than that of commercial Pt/C catalyst (33.1 mA·cm-2). Tests with real urine at 20 mA cm-2 achieve 74% total nitrogen removal and 2853 µmol·h-1 of H2 production. This study provides an attractive landscape for producing H2 by consuming urine biowastes.

The Effects of Chronic Lead Exposure on Testicular Development of Japanese Quail (Coturnix japonica): Histopathological Damages, Oxidative Stress, Steroidogenesis Disturbance, and Hypothalamus-Pituitary-Testis Axis Disruption.

Lead (Pb) becomes a global public health concern for its high toxicology. Birds are sensitive to environmental pollution and Pb contamination exerts multiple negative influences on bird life. Pb also impacts on avian reproductive system. Thus, in this study, we attempted to determine toxicological effects and possible mechanistic pathways of Pb on avian testicular development by using the model species-Japanese quail (Coturnix japonica). Male quail chicks of 1-week-old were exposed to 0, 50, 500, and 1000 ppm Pb concentrations in drinking water for 5 weeks when reaching sexual maturation. The results showed that high Pb doses (500 and 1000 ppm) induced testis atrophy and cloacal gland shrinkage. Microstructural damages of both hypothalamus and testis indicated the disruption of the hypothalamus-pituitary-gonadal (HPG) axis by Pb exposure. The decrease of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and testosterone (T) may also imply HPG axis disruption. Moreover, excess testicular oxidative damages featured by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) and decreasing catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), and total antioxidant capacity (T-AOC) indicated increasing risks of reproductive dysfunction by Pb. Furthermore, increasing apoptosis and upregulation of gene expression associated with cell death suggested testicular abnormal development. In addition, molecular signaling involved with steroidogenesis in the testis was disturbed by Pb treatment. The study showed that Pb could impair testicular development and reproductive function by morphological and histological injury, hormone suppression, oxidative stress, cell death, and HPG axis disruption.

Lead induced disorders of lipid metabolism and glycometabolism in the liver of developmental Japanese quails (Coturnix japonica) via inhibiting PI3K/Akt signaling pathway.

The lead (Pb) contamination is considered a lethal threat to birds. However, Pb-induced hepatotoxicology especially its impacts on metabolic processes in the liver of birds is not yet fully understood. Therefore, we tried to determine the toxicological effects of Pb exposure on hepatic carbohydrate and lipid metabolism via Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway by using an animal model- Japanese quail (Coturnix japonica). One-week old female Japanese quails were randomly allocated into four groups and fed with 0, 50 ppm, 500 ppm and 1000 ppm Pb drinking water respectively for 49 days. The results showed that Pb accumulated in the liver as a dose-dependent manner. Exposure to high dose of Pb (500 and 1000 ppm Pb) led to severe histopathological damages characterized by irregularity and dilation of liver sinusoids, hepatic lipid vacuolization and hepatocellular cytoplasm hyalinization. Meanwhile, Pb exposure caused glycogen increase and lipid droplets decrease in the liver. Pb exposure was also attributable to a decreased triglyceride level in the plasma. In addition, the transcriptional levels of PI3K and Akt in the liver were downregulated by Pb exposure. Subsequently, the mRNA expressions of genes related with glycometabolism in the liver were remarkably altered and the mRNA levels of genes involved in fat synthesis and oxidation in the liver were also markedly changed. it seems that Pb could lead to liver metabolic disorder through structural damages and PI3K/Akt signaling pathway disruption.

Surveillance of occupational exposure to blood-borne pathogens among medical workers in a tertiary general hospital from 2010 to 2022 / 预防医学

Objective @#To investigate the occupational exposure to blood-borne pathogens among medical workers in a tertiary general hospital in Hangzhou City from 2010 to 2022, so as to provide the evidence for improving occupational protective measures among medical workers.@*Methods@#The registration and follow-up data of occupational exposure to blood-borne pathogens among medical workers from 2010 to 2022 were collected from the blood-borne occupational exposure monitoring system in a tertiary general hospital in Hangzhou City. The population distribution, occurrence, protection and disposal of occupational exposure to blood-borne pathogens were analyzed using a descriptive epidemiological method.@*Results@#A total of 1 230 cases were reported with occupational exposure to blood-borne pathogens among medical workers in the study hospital from 2010 to 2022, with the highest incidence in 2021 (4.67%) and the lowest incidence in 2010 (0.99%). The incidence of occupational exposure to blood-borne pathogens appeared a tendency forwards a rise from 2010 to 2022 (P<0.05). Of all cases with occupational exposure to blood-borne pathogens, there were 934 women (75.93%), 656 nurses (53.33%), and 514 cases with working experiences of one year and shorter (41.79%). Hand was the predominant site of occupational exposure to blood-borne pathogens (92.03%) and ward was the predominant place of exposure (35.37%), while scalp needle was the predominant mode of exposure (32.68%), and removal of needle was the predominant procedure of exposure (32.36%). A total of 1 106 cases were tested for the blood-borne pathogens in the exposure sources, and 448 cases were tested positive for blood-borne pathogens, with a detection rate of 40.51%. Hepatitis B virus, treponema pallidum and human immunodeficiency virus were the three most common blood-borne pathogens, and there were 739 cases (60.08%) with personal protective equipment during exposure. Following the follow-up surveillance for more than 6 months post-exposure, no infections occurred. @*Conclusions@#Junior nurses and hand exposure were predominant among medical workers with occupational exposure to blood-borne pathogens in the study hospital from 2010 to 2022, and hepatitis B virus was the predominant blood-borne pathogen. No post-exposure infections occurred.

Lead induced thymic immunosuppression in Japanese quail (Coturnix japonica) via oxidative stress-based T cell receptor pathway signaling inhibition.

The human-induced lead (Pb) contamination brings about serious environmental issues around the world and it also poses severe risks to wildlife including birds. Avian thymus is one of primary lymphoid organs and it plays an important role in regulating T cell-based cellular immunity. Therefore, in this study, we tried to examine toxic effects and potential molecular mechanism of Pb on avian thymus using a biological model species-Japanese quail (Coturnix japonica). One-week-old Japanese quails were exposed to 0, 50, 500 and 1000 ppm Pb concentrations in drinking water for three weeks when thymus reached developmental climax. The results showed body weight, thymus weight and thymic size were reduced significantly by Pb exposure. Meanwhile, histopathological changes including vacuolation, cortex atrophy and nuclear debris were detected in thymic cells of Pb exposure. In addition, ultrastructural alterations such as mitochondrial damage, chromatin condensation, and nuclear destruction were found in the thymus of Pb treatments. The increase of reactive oxygen species (ROS) and Malondialdehyde (MDA) as well as the inhibition of antioxidant system indicated that Pb exposure caused oxidative damages in the thymus. Pb exposure also increased thymic cell apoptosis. Moreover, RNA-Seq analysis revealed that thymic functional pathways were disrupted by Pb exposure. Especially, Pb exposure disturbed T cell differentiation and led to T helper type 1 (Th1) /T helper type 2 (Th2) imbalance by interfering with T cell receptor signaling and cytokine signaling. This study implied that Pb caused thymic immunosuppression through causing morphological deformation, structural destruction, oxidation and molecular signaling disruption.

Transcriptomic Analysis of Hepatotoxicology of Adult Zebrafish (Danio rerio) Exposed to Environmentally Relevant Oxytetracycline.

The extensive use of the broad-spectrum antibiotics like oxytetracycline (OTC) has become a serious environmental issue globally. OTC has profound negative effects on aquatic organisms including fishes. In this study, RNA-Seq analysis was employed to examine the possible molecular mechanism of hepatotoxicology in zebrafish induced by OTC exposure. Adult male zebrafish was exposed to 0, 5, 90, and 450 µg/L OTC for 3 weeks. The results showed the decrease in body weight and tail length but the increase in total length of zebrafish under OTC exposure in a dose-dependent way. In addition, severe histopathological damages were featured by increasing tissue vacuolization in the livers of 450 µg/L OTC group. Moreover, RNA-Seq analysis revealed that molecular signaling and functional pathways in the liver were disrupted by OTC exposure. Furthermore, the down-regulation of gene expression after OTC exposure was found on both the genes related to fatty acid degradation and the genes related to lipid synthesis. The present study implied that OTC induced liver malfunction and fish health risks through growth retard, histopathological damages, molecular signaling disruption, genetic expression alteration, and lipid metabolism disturbance.

Exposed to Sulfamethoxazole induced hepatic lipid metabolism disorder and intestinal microbiota changes on zebrafish (Danio rerio).

Antibiotics are widely used around the world. Pollution of Sulfamethoxazole (SMX) in water poses a great threat to aquatic life. In this study, the toxic effects of SMX on the liver were assessed through RNA sequencing analysis and 16S rRNA sequencing analysis was conducted to determine the influence of SMX on gut microbiota of zebrafish (Danio rerio). Adult male zebrafish were exposed to 0, 5, 90 and 450 µg/L of environmentally relevant concentrations of SMX for 21 days respectively. The results showed that the liver had severe histopathological damages including pyknotic nuclei, cytoplasmic hyalinization and vacuolization and deformed hepatocytes with loose cell-to-cell contact. Transcriptomic analysis revealed that liver function was seriously affected by SMX exposure. Meanwhile, SMX exposure significantly inhibited the expression of genes associated with fatty acid synthesis, oxidation and transport. Besides, exfoliated and dissolved epithelial cells were observed in the gut after SMX treatment. Although there was no significant change on richness and species diversity of intestinal microbial community, the relative abundance of phylum and genus of SMX treatments were significantly different from that of control group. The present study implied that SMX may cause potential health risks to fish through inducing histopathological damages, genetic expression alterations, disorder of fatty acid metabolism and intestinal microbiota dysbiosis.

Cadmium induced cardiac toxicology in developing Japanese quail (Coturnix japonica): Histopathological damages, oxidative stress and myocardial muscle fiber formation disorder.

The anthropogenic-induced cadmium (Cd) pollution poses great threats to human health and wildlife survival. Birds also suffer from Cd contamination and Cd exerts negative impacts on multiple organs in birds. However, its toxic effects on cardiac organ of birds are still unclear. In this study, one-week old male Japanese quails were exposed to 15, 30, 60 and 75 mg/kg Cd for 5 weeks when birds in control group reached sex maturity. The results showed that Cd could cause microstructural damages including congestion and myocardial fiberolysis. Ultrastructural analysis also showed myocardial muscle fiber disarrangement and rupture as well as mitochondrial swelling, vacuolation and membrane lysis in Cd concentration groups. Moreover, Cd induced oxidative stress in the heart by decreasing antioxidant enzyme activities of catalase (CAT), glutathione peroxidase (GPX), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) while increasing oxidative biomarkers such as malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and content of nitric oxide (NO). In addition, mRNA expression levels of genes involved in muscle fiber formation signaling pathway such as Follistatin (FST), paired box 3 (PAX3), myogenic differentiation 1 (MYoD1) and SRY-box transcription factor 6 (SOX6), were down-regulated by Cd exposure. Furthermore, PI3K/Akt/mTOR signaling pathway were disrupted by Cd exposure implying energy supply deficiency in the heart. We concluded that Cd caused cardiac dysfunction by inducing heart underdevelopment, histopathological injury, oxidative stress and myocardial muscle fiber formation disruption.

Lead exposure induced inflammation in bursa of Fabricius of Japanese quail (C. japonica) via NF-κB pathway activation and Wnt/ß-catenin signaling inhibition.

Bursa of Fabricius (BF), one of primary lymphoid organ, is unique to birds. Meanwhile, lead (Pb) is well known for its high toxicology to birds. Therefore, this study aimed to examine the chronic toxic effects of lead exposure on BF in Japanese quails (C. japonica) and the underlying mechanism of lead immunotoxicity. One-week old male quails were exposed to 0 ppm, 50 ppm, 500 ppm and 1000 ppm Pb concentrations by drinking water for four weeks. The results showed that Pb accumulation in BF increased in a dose dependent way. The growth and development of BF was retarded in 500 ppm and 1000 ppm Pb groups. The number of lymphocytes was decreased and the release of immunoglobulin G and M (IgG, IgM), complement 3 and 4 (C3, C4) was inhibited by Pb exposure. Lead exposure also caused oxidative stress and increasing apoptosis in BF. Moreover, histopathological damages characterized by inflammatory hyperemia and inflammatory cell infiltration and ultrastructural injury featured by mitochondrial vacuole, cristae fracture and chromatin concentration were found in BF of 500 ppm and 1000 ppm Pb groups. Furthermore, RNA sequencing based transcriptomic analysis revealed that molecular signaling and functional pathways in BF were disrupted by lead exposure. In addition, the activation of Nuclear Factor kappa B (NF-κB) pathway while the inhibition of wingless integrated/catenin beta 1 (Wnt/ß-catenin) signaling by Pb exposure were confirmed by quantitative real-time PCR (qPCR). Our study may benefit to understand potential mechanistic pathways of developmental immunotoxicology under Pb stress.

Downregulation of SOX2-OT Prevents Hepatocellular Carcinoma Progression Through miR-143-3p/MSI2.

OBJECTIVE: LncRNA SOX2-OT is involved in a variety of cancers. This study explored the effect of lncRNA SOX2-OT on hepatocellular carcinoma (HCC) cells. METHODS: SOX2-OT expressions were detected in HCC tissues and normal tissues, normal cells, and HCC cells. The relationship between SOX2-OT and prognosis was analyzed by TCGA. After SOX2-OT expression was inhibited using siRNA, HCC cell malignant behaviors were evaluated. The subcellular localization of SOX2-OT in HCC cells was predicted and analyzed. The binding relationships among SOX2-OT, miR-143-3p, and MSI2 were analyzed by bioinformatics website, dual-luciferase assay, and RNA pull-down assay. The effect of miR-143-3p and MSI2 on the regulation of SOX2-OT on biological behaviors of HCC cells was confirmed by functional rescue experiments. The effect of SOX2-OT on the tumorigenicity of HCC was evaluated by subcutaneous tumorigenesis in nude mice. RESULTS: SOX2-OT was highly expressed in HCC cells and tissues. The prognosis was poor in HCC patients with high SOX2-OT expression. Downregulating SOX2-OT inhibited HCC cell malignant behaviors. SOX2-OT bound to miR-143-3p to promote MSI2 expression. Downregulating miR-143-3p or upregulating MSI2 averted the role of si-SOX2-OT in HCC cells. Nude mouse subcutaneous tumorigenesis showed that SOX2-OT downregulation decreased the tumorigenicity of HCC, and affected the levels of miR-143-3p and MSI2 mRNA in tumor tissues. CONCLUSION: SOX2-OT inhibited the targeted inhibition of miR-143-3p on MSI2 through competitively binding to miR-143-3p, thus promoting MSI2 expression and proliferation, invasion, and migration of HCC cells.

Transcriptomic analysis of lead-induced hepatoxicology in female Japanese quails (Coturnix japonica): Implications of triglyceride synthesis, degradation and transport disruption.

Lead (Pb) pollution poses great threats to mammals including human and it is also hazardous to bird life. In this study, RNA sequencing analysis was employed to examine the molecular responses to lead exposure in the liver of a toxicological model species Japanese quails (Coturnix japonica). Female birds were exposed to 0, 50, 500 and 1000 ppm waterborne Pb for 49 days. The results showed that hepatic microstructure was damaged under lead exposure featured by sinusoids dilation and irregularity as well as cell necrosis. Moreover, ultrastructural injury in the liver including mitochondrial swelling and vacuolization as well as nuclear deformation was induced by lead exposure. Lead exposure also caused the decrease of lipid droplets in the liver by oil red O staining. In addition, liver transcriptomic analysis revealed that molecular signaling and functional pathways were disrupted by lead exposure. Meanwhile, the expression of genes involved with hepatic glycerophospholipids metabolism of triglyceride synthesis and lipid transport of triglyceride transfer was significantly down-regulated by lead exposure. Moreover, the up-regulation of genes associated with fatty acid oxidation and the down-regulation of genes related with fatty acid synthesis were caused by lead exposure. The present study implied that lead induced liver malfunction and bird health risks through histopathological damages, molecular signaling disruption, genetic expression alteration and triglyceride metabolism disturbance.

Cadmium induced skeletal underdevelopment, liver cell apoptosis and hepatic energy metabolism disorder in Bufo gargarizans larvae by disrupting thyroid hormone signaling.

Cadmium (Cd) is hazardous to human health and it is also highly detrimental to amphibian life. In this study, Bufo gargarizans larvae were exposed to environmentally relevant Cd concentrations of 5, 100 and 200 µg L-1 from Gosner stage (Gs) 26 to Gs 42 of metamorphic climax about 6 weeks. The results showed thyroid structural injuries and thyroid signaling disruption were induced by high Cd exposure (100 and 200 µg L-1). Moreover, tadpole skeleton including whole body, vertebrata, forelimb and hindlimb was developmentally delayed by high Cd exposure through downregulating the mRNA expressions of genes involved with skeletal ossification and growth pathway. Moreover, liver histopathological injuries were caused by high Cd exposure featured by hepatocytes malformation, nuclear degeneration and increasing melanomacrophage centers. Meanwhile, liver apoptosis rate showed on the rise in a dose-dependent way and Cd stimulated liver apoptosis by upregulating mRNA expressions of genes related to extrinsic and intrinsic apoptosis pathways. Furthermore, high Cd caused hepatic glucometabolism disorder by decreasing the genetic expressions associated with glycolysis and mitochondrial oxidative phosphorylation. In addition, liver lipid metabolism was disrupted by high Cd exposure through downregulating mRNA levels of genes related to fatty oxidation and upregulating mRNA levels of genes related to fatty acid synthesis. We suggested that Cd did great harm to tadpole health by disturbing thyroid function, skeletal growth, liver cell apoptosis signaling and hepatic energy metabolism pathway.

The effects of chronic lead exposure on the ovaries of female juvenile Japanese quails (Coturnix japonica): Developmental delay, histopathological alterations, hormone release disruption and gene expression disorder.

Lead (Pb) is well-recognized for its great hazards to human and wildlife health. It has negative influences on multiple organs and systems of birds. Especially, lead exposure caused adverse impacts on bird reproduction. In this study, one week old female Japanese quails were randomly allocated into four groups and each group was respectively fed with 0, 50 ppm, 500 ppm and 1000 ppm Pb in drinking water for 36 days to determine the effects of chronic lead exposure on ovarian development and function. The results showed that Pb did accumulate in the ovary and ovarian development was delayed by high dose lead exposure (500 ppm and 1000 ppm). Moreover, high Pb dosage induced ovarian histopathological damages characterized by granulosa cells disorganization, follicle atresia and interstitial cell degeneration. Meanwhile, the concentration of estradiol (E2) was significantly decreased and mRNA levels of genes involved with ovarian steroidogenesis were significantly down-regulated by high concentration Pb. In addition, Pb exposure caused increasing cell apoptosis and significant changes of the expression of genes involved with cell death in the ovary. High dose Pb exposure also inhibited thyroid hormone release and disrupted ovarian thyroid deiodination apart from causing thyroid histopathological injury such as follicular deformation and atrophy. The study indicated that Pb might cause ovarian malfunction by inducing ovary and thyroid microstructural damages, thyroid hormone and estrogen release inhibition and ovarian steroidogenesis disruption.