Exploration of the Components and Pharmacological Mechanisms of Keyin Pill-Induced Liver Injury Based on Network Pharmacology.

Background: Keyin pill (KP), a patented medicine in China, is used to treat psoriasis. However, KP has been reported to have liver toxicity, but its toxic substance basis and underlying mechanisms remain unclear. Therefore, this study aimed to explore the pharmacological mechanisms and components of KP-induced liver injury through animal experiments, UPLC-QTOF/MS combined with network pharmacology.

Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway.

Background: Hypothermia is a complex pathophysiological response that can be life-threatening in low-temperature environment because of impaired thermoregulation. However, there is currently no clinically effective drugs that can prevent or treat this disease. Brown adipose tissue (BAT) activation or browning of white adipose tissue (WAT) is a promising therapeutic strategy to prevent or treat hypothermia.

[Establishment of spectrum-effect relationship network model of qizhiweitong granules promoting gastrointestinal motility].

Objective: To establish the spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility for providing scientific basis for its quality control and efficacy evaluation.

Methods: The Latin hypercube sampling was used to establish full-time multi-wavelength fusion fingerprints of different compatibility groups of Qizhiweitong granules. At the same time, the appreciation rate, the contents of cGMP and NO in small intestine smooth muscle cells after administrated drugs were determined.

Molecular mechanisms of nanosized titanium dioxide-induced pulmonary injury in mice.

The pulmonary damage induced by nanosized titanium dioxide (nano-TiO2) is of great concern, but the mechanism of how this damage may be incurred has yet to be elucidated. Here, we examined how multiple genes may be affected by nano-TiO2 exposure to contribute to the observed damage. The results suggest that long-term exposure to nano-TiO2 led to significant increases in inflammatory cells, and levels of lactate dehydrogenase, alkaline phosphate, and total protein, and promoted production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse lung tissue.

Cerium chloride improves protein and carbohydrate metabolism of fifth-instar larvae of Bombyx mori under phoxim toxicity.

The organophosphorus pesticide poisoning of the silkworm Bombyx mori is one of the major events causing serious damage to sericulture. Added low-dose rare earths are demonstrated to increase resistance in animals. However, very little is known about whether or not added CeCl₃ can increase resistance of silkworm to phoxim poisoning.

Titanium dioxide nanoparticles relieve biochemical dysfunctions of fifth-instar larvae of silkworms following exposure to phoxim insecticide.

Phoxim insecticide is widely used in agriculture, which is toxic to insect pests and nontarget organisms. The phoxim poisoning is hard to prevent for silkworms. TiO(2) NPs have been widely applied in whitening, brightening foods, toothpaste or sunscreens, and orally-administered drugs.

Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice.

Although liver toxicity induced by titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO(2) NPs for 90 days. The findings showed that long-term exposure to TiO(2) NPs resulted in obvious titanium accumulation in the liver and TiO(2) NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction.

MicroRNA-1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma.

A short tandem repeat (STR) polymorphism in the 3'UTR region of esophageal cancer-related gene 2 (ECRG2, also known as SPINK7) has been widely reported to be associated with the incidence and the prognosis of esophageal squamous cell carcinoma (ESCC). This study explores how the microRNA binding to the STR region affects ECRG2 expression in ESCC. Dual-luciferase reporter assays were used to verify the effects of the four microRNAs (miR-580, miR-1182, miR-1272, and miR-1322) predicted to bind the STR region of the ECRG2 3' untranslated region (UTR).

The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles.

To understand the chronic spleen injury induced by intragastric administrations with 2.5, 5, and 10 mg kg(-1) body weight titanium dioxide nanoparticles (TiO(2) NPs) for 90 consecutive days, histopathological and ultrastructure changes, hematological parameters, lymphocyte subsets, the inflammatory, and apoptotic cytokines in the mouse spleen were investigated. Our findings indicate that TiO(2) NPs exposure results in the significant increase in the spleen indices, histopathological changes, and splenocyte apoptosis in spleen.

Effects of added CeCl3 on resistance of fifth-instar larvae of silkworm to Bombyx mori nucleopolyhedrovirus infection.

One of the most important agents causing lethal disease in the silkworm is the Bombyx mori nucleopolyhedrovirus (BmNPV), while low-dose rare earths are demonstrated to increase immune capacity in animals. However, very little is known about the effects of added CeCl(3) on decreasing BmNPV infection of silkworm. The present study investigated the effects of added CeCl(3) to an artificial diet on resistance of fifth-instar larvae of silkworm to BmNPV infection.

Immune dysfunction and liver damage of mice following exposure to lanthanoids.

In an effort to investigate the effects of exposure to lanthanoids (Ln) on the immune response and liver function, mice were orally exposed to LaCl3 , CeCl3 , and NdCl3 at 2, 10, and 20 mg/kg doses for 30 days, respectively; lymphocyte counts, serum IgM level, hematological indices, biochemical parameters of liver functions, and histopathological changes in Ln(3+) -treated mice were assessed. Indeed, 20 mg/kg Ln(3+) significantly inhibited mice growth and reduced the counts of white blood cells, platelets, and reticulocyte in mice blood. Specifically, in these Ln(3+) -treated mice, CD3+, CD4+, CD8+, CD19+ and NK cells, and CD4+/CD8+ ratio as well as serum IgM level were decreased.

Molecular mechanism of kidney injury of mice caused by exposure to titanium dioxide nanoparticles.

Numerous studies have demonstrated that damage of kidney of mice can be caused by exposure to titanium dioxide nanoparticles (TiO(2) NPs). However, the molecular mechanism of TiO(2) NPs-induced nephric injury remains unclear. In this study, the mechanism of nephric injury in mice induced by an intragastric administration of TiO(2) NPs was investigated.

The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma.

miR-31 (microRNA-31) is frequently altered in numerous cancers. The aim of the present study was to investigate the role of miR-31 in ESCC (oesophageal squamous cell carcinoma). We measured miR-31 in 45 paired ESCC tissues and 523 serum samples using real-time RT (reverse transcription)-PCR.

Molecular mechanism of inflammatory response in mouse liver caused by exposure to CeCl₃.

To investigate the molecular mechanism of inflammatory response in the mouse liver caused by exposure to CeCl₃, we measured the liver indices, and cerium content, evaluated the liver histopathological section, detected serum biochemical parameters of liver function, and the immunoglobulin M (IgM) content, analyzed the liver mRNA and protein expression levels of Toll-like receptor 2, 4 (TLR2, TLR4), and inflammatory cytokines in liver using real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that exposure to CeCl₃ decreased body weight and caused cerium accumulation in the mouse liver and histopathological changes of liver (such as inflammatory cell infiltration). Furthermore, biochemical assays suggested that CeCl3 could promote the activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, pseudocholinesterase, and leucine aminopeptidase, decrease serum IgM, upregulate the levels of TLR2, TLR4, nuclear factor-κB (NF-κB), NF-κBp52, NF-κBp65, NF-κB-inducing kinase (NIK), IκB kinase α (IKK-α), IκB kinase β (IKK-β), and tumor necrosis factor-α (TNF-α) expression, and suppress NF-κB-inhibiting factor (IκB) and interleukin-2 (IL-2) expression in liver.

Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles.

Previous studies demonstrate that the exposure to titanium dioxide nanoparticles (TiO(2) NPs) damages the central nervous system of mice; however, very little is known about the effects of TiO(2) NPs on hippocampal apoptosis or its molecular mechanism. The present study investigated the molecular mechanism associated with hippocampal apoptosis in mice induced by intragastric administration of TiO(2) NPs for consecutive 60 days. Our findings indicate that TiO(2) NPs accumulate in the mouse hippocampus, and this accumulation, in turn, led to hippocampal apoptosis and impairment in spatial recognition memory in mice.

Liver injury and its molecular mechanisms in mice caused by exposure to cerium chloride.

Cerium has been demonstrated to damage liver of mice, but very little is known about the molecular mechanisms underlying the mouse liver apoptosis. In order to understand the liver injury induced by intragastric administration of cerium chloride (CeCl3) for 60 consecutive days, the hepatocyte ultrasrtucture, various oxidative stress parameters, and the stress-related gene expression levels were investigated for the mouse liver. The results demonstrated that CeCl3 had an obvious accumulation in the mouse liver, leading to a classical laddering cleavage of DNA and hepatocyte apoptosis.

The toxicological effects in brain of mice following exposure to cerium chloride.

Cerium (Ce) compounds are now widely applied in medicine, agriculture, animal breeding, and daily life; however, the effects of Ce on human body, especially on the central nervous system, are still unclear. In order to investigate whether Ce exposure cause neurotoxicological effects, ICR mice were exposed to CeCl(3) through intragastric administration at 0, 2, 10, and 20 mg/kg body weight doses everyday for 60 days. The behaviors of spatial recognition memory, brain histopathology, the brain elements and neurochemicals, as well as enzymes activities in mice were determined.

[Immediately effects of inhaled aerosolised iloprost in adult patients with severe pulmonary hypertension secondary to congenital heart diseases].

Objective: To investigate the immediately effects of inhaled aerosolized iloprost in adult patients with severe pulmonary arterial hypertension (PAH) secondary to congenital heart diseases (CHD).

Methods: Adult patients with severe PAH secondary to CHD (n = 165) were included in this study. Right heart catheterization was performed, Pulmonary and systemic blood flow, the oxygen consumption VO(2) (ml/min) were calculated using Fick's principle.

Signal pathway of hippocampal apoptosis and cognitive impairment of mice caused by cerium chloride.

Experimental studies have demonstrated that lanthanides could impair cognitive functions of children and animals, but very little is known about the hippocampal apoptosis and its molecular mechanism. The study investigated the signal pathway of hippocampal apoptosis induced by intragastric administration of CeCl(3) for 60 consecutive days. It showed that cerium had been significantly accumulated in the mouse hippocampus, and CeCl(3) caused hippocampal apoptosis and impairment of spatial recognition memory of mice.

WITHDRAWN: Mechanism of inflammatory responses in brain and impairment of spatial memory of mice caused by titanium dioxide nanoparticles.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.

Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles.

In an effort to examine signaling pathway of inflammation of the mouse liver caused by intragastric administration of titanium dioxide nanoparticles (NPs), we assessed Toll-like receptor-2 (TLR2), TLR-4, IκB kinase (IKK-α, IKK-β), IκB nucleic factor-κB (NF-κB), NF-κBP52, NF-κBP65, tumor necrosis factor-α (TNF-α), NF-κB-inducible kinase (NIK), interleukin-2 (IL-2), biochemical parameters of liver functions, and histopathological changes and liver ultrastructure in the TiO(2) NPs-treated mice. The results showed the titanium accumulation in liver, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by TiO(2) NPs. The real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay analyses showed that TiO(2) NPs can significantly increase the mRNA and protein expression of TLR2 and TLR4 and several inflammatory cytokines, including IKK1, IKK2, NF-κB, NF-κBP52, NF-κBP65, TNF-α, and NIK, and TiO(2) NPs can significantly decrease the mRNA and protein expression of IκB and IL-2.

Hepatocyte apoptosis and its molecular mechanisms in mice caused by titanium dioxide nanoparticles.

While the hepatocyte apoptosis induced by TiO(2) nanoparticles (NPs) has been demonstrated, very little is known about the molecular mechanisms underlying this mouse liver apoptosis. In order to understand the hepatocyte apoptosis induced by intragastric administration of TiO(2) NPs for consecutive 60 days, the hepatocyte apoptosis, various oxidative stress parameters and the stress-related gene expression levels were assayed for the mouse liver. 60 days of TiO(2) NPs exposure, hepatocyte apoptosis in the liver could be observed, which was followed by increased reactive oxygen species accumulation, and decreased the stress-related gene expression levels of superoxide dismutase, catalase, glutathione peroxidase, metallothionein, heat shock protein 70, glutathione S transferase, P53, and transferrin; and the significant enhancement of the cytochrome p450 1A expression level.

Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles.

Titanium dioxide nanoparticles (TiO(2) NPs) are now in daily use including popular sunscreens, toothpastes, and cosmetics. However, the effects of TiO(2) NPs on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether TiO(2) NPs exposure results in persistent alternations in nervous system function.