Tumour necrosis factor-α-induced protein 8-like 2 is a novel regulator of proliferation, migration, and invasion in human rectal adenocarcinoma cells.

Tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non-tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down-regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down-regulating the expression levels of Wnt3a, phospho (p)-ß-Catenin, and p-glycogen synthase kinase-3ß in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p-Smad2, p-Smad3, and transforming growth factor-beta (TGF-ß) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/ß-Catenin and TGF-ß/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.

PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways.

BACKGROUND: PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. METHODS: ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. RESULTS: PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. CONCLUSIONS: PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.

A cross-sectional analysis of prescription and stakeholder surveys following essential medicine reform in Guangdong Province, China.

BACKGROUND: An essential medicine (EM) system has been implemented in China to reduce patients' financial burden and to make the use of drugs more rational. This study aims to evaluate the current state of the EM system in Guangdong Province. METHODS: We conducted surveys in 21 cities in 2012, covering 98 medical institutions, 1,509 doctors, 17 medicine manufacturers, and 17 distribution companies. We also reviewed outpatient prescriptions (n = 9,941) for treating hypertension, diabetes, bacterial infections and gout to measure the rational use of drugs in secondary and tertiary (upper-level) hospitals. RESULTS: The percentage of non-priority EM use ranged from 8.1% to 10.7% in upper-level hospitals, and this non-priority use significantly increased prescription drug costs. Other types of inappropriate medicine use were found more frequently in treating bacterial infections (7.4%) than in treating hypertension (1.6%), diabetes (1.3%) and gout (1.7%). Tertiary hospitals prescribed fewer EMs than secondary hospitals; moreover, tertiary hospitals had higher prescription drug costs. The zero mark-up policy decreased prescription drug costs in secondary hospitals. The survey revealed that forced full-prescription EM use might lead to fewer patient visits to primary hospitals. Manufacturers had halted the production of four (1, 23) types of EMs at the time of the survey. CONCLUSIONS: Encouraging the priority use of EMs and implementation of the zero mark-up policy were effective in curtailing prescription medicine costs in upper-level hospitals. Further work should focus on the following: creating guidelines to enhance rational prescription behavior, establishing policies to support EM use in upper-level hospitals and improving the bidding system to ensure a steady supply of the lowest-priced generic drugs.

Comparison of virulence properties of Pseudomonas aeruginosa exposed to water and grown in rich broth.

Pseudomonas aeruginosa is an opportunistic pathogen that can infect susceptible patients suffering from cystic fibrosis, immunosuppression, and severe burns. Nosocomial- and community-acquired infection is likely due to contact with water sources contaminated with P. aeruginosa. Most of what is known about the virulence properties of P. aeruginosa was derived from studies using fairly rich broths, which do not represent conditions found in water, such as low nutrient concentrations. Here, we compare biofilm production, invasion of epithelial cells, cytotoxicity, and pyocyanin production of P. aeruginosa in water with P. aeruginosa grown in rich broth. Since tap water is variable, we used a defined water medium, Fraquil, to ensure reproducibility of the results. We found that P. aeruginosa does not readily form biofilm in Fraquil. Pseudomonas aeruginosa is equally able to attach to and invade epithelial cells but is more cytotoxic after incubation in water for 30 days than when it is grown in rich broth. Moreover, P. aeruginosa produces less pyocyanin when exposed to water. Our results show that P. aeruginosa seems to have different properties when exposed to water than when grown in rich broth.

[Treatment of antipsychotic drug-induced phlegm dampness type amenorrhea by Wuji Powder and a small dose aripiprazole: a clinical study].

OBJECTIVE: To assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea. METHODS: Seventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group, 35 in each group. All patients received antipsychotic drug therapy. Patients in the treatment group additionally took WP, while those in the control group took aripiprazole (at the daily dose of 5 mg, once daily). The therapeutic course for all was 4 weeks. Prolactin levels and obesity indices[body weight, waist aircumstance, body mass index (BMI) and waist-hit ratio (WHR)] were determined before and after treatment. The efficacy was evaluated. RESULTS: The treatment course was completed in 95.71% of patients. The total effective rate of the 33 patients of the treatment group was 93.94% (31/33), while it was 91.18% (31/34) in the 34 patients of the control group. There was no difference in the total effective rate between the two groups (P > 0.05). Prolactin levels in both group after treatment were significantly lower than those of the baseline (P < 0.01). There was no significant difference in prolactin levels between the two groups after treatment (P > 0.05). Compared with before treatment, body weight, BMI, waist circumstance, and waist-hip ratio obviously decreased after treatment, showing significant difference when compared with the control group (P < 0.05). There was no significant difference in body weight, BMI, waist circumstance, and waist-hip ratio in the control group between before and after treatment (P > 0.05). CONCLUSIONS: Both WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea. They showed equivalent efficacy. But WP showed more obvious effect in reducing obesity indices.

Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF. METHODS: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) staining. Mitochondrial morphology was detected by MitoTracker® Deep Red FM or transmission electron microscopy (TEM). Western blotting and immunofluorescence were used to determine the expression of protein. The migration ability of the cells was detected by the cell scratch test. Mitochondrial DNA (mtDNA) levels were assessed by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect cytokine levels. Superoxide dismutase (SOD) activity and the levels of glutathione (GSH) and malondialdehyde (MDA) were detected by chemichromatometry. RESULTS: PQ exposure caused EMT and PF in vivo and in vitro. PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1 (Drp1), which were accompanied by oxidative stress. Inhibiting mitochondrial fission using mitochondrial division inhibitor-1 (Mdivi-1), a selective inhibitor of Drp1, attenuated PQ-induced EMT and oxidative damage. Treatment with N-acetyl-L-cysteine (NAC), an antioxidant, reduced Drp1 expression, attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF. Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release, the expression of Toll-like receptor 9 (TLR9) and phosphorylation (P)-NF-κB p65 as well as cytokines (interleukin 6 [IL-6], interleukin-1ß [IL-1ß], and tumor necrosis factor-α [TNF-α]) production. CONCLUSION: Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF, which is associated with the mtDNA/TLR9/NF-κB pathway.

PCNP is a novel regulator of proliferation, migration, and invasion in human thyroid cancer.

Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/ß-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion, in vitro and in vivo data demonstrate that PCNP as a tumor suppressor gene may serve as a novel prognostic and potential therapeutic marker in human thyroid cancer.

Takotsubo cardiomyopathy associated with adrenal insufficiency in the context of long-term steroid use mimicking acute coronary syndrome.

Takotsubo cardiomyopathy (TCMP) is an important, though under-recognised, syndrome which mimics acute coronary syndrome (ACS) presenting with similar clinical, biochemical and ECG features. A 68-year-old man was referred as ACS for emergency coronary angiography; however, a history of lethargy, weight loss and electrolyte abnormalities prompted further investigations. Angiography was postponed, adrenal insufficiency confirmed and steroid replacement commenced. Echocardiography demonstrated reduced left ventricular (LV) function (45%) with regional wall motion abnormalities, although angiography confirmed unobstructed arteries. Steroid replacement induced a rapid improvement in symptoms and LV function. Few cases of TCMP associated with adrenal insufficiency have been reported. This appears to be the first case describing TCMP precipitated by new-onset secondary adrenal insufficiency following long-term steroid use in a male patient, and highlights the importance of considering TCMP in patients presenting with suspected ACS. Here, prompt recognition and treatment of a serious underlying disorder prevented a potentially life-threatening Addisonian crisis.

[A survey of mental health among transferred injured survivors in Wenchuan earthquake in Sichuan].

OBJECTIVE: To assess the depression and anxious status among transferred injured survivors in Wenchuan earthquake in Sichuan province. METHODS: A total of 43 transferred injured survivors were investigated by questionnaire exploring their trauma symptoms and mental health status. RESULTS: High rates of trauma symptoms were remarkably observed in these survivors. Of all the respondents, 60% had some emotional symptoms and sleeping difficulties. About one third of respondents experienced recurrent and intrusive distressing recollection of event, 16 (37.21%) experienced nightmare, 15 (34.88%) had flashback and 7 (16.28%) of them tried to avoid relative stress. CONCLUSION: Many mental symptoms were observed in transferred injured survivors. The two major factors of mental stress were emotional symptoms and re-experience of the disaster.

PEST-containing nuclear protein regulates cell proliferation, migration, and invasion in lung adenocarcinoma.

Lung cancer is the leading cause of cancer-related mortality worldwide. PEST-containing nuclear protein (PCNP) has been found in the nucleus of cancer cells. Whether PCNP plays a role in the growth of lung adenocarcinoma is still unknown. In the present study, the results indicated that the level of PCNP in lung adenocarcinoma tissue was significantly higher than that in corresponding adjacent non-tumor tissue. Over-expression of PCNP promoted the proliferation, migration, and invasion of lung adenocarcinoma cells, while down-regulation of PCNP exhibited opposite effects. PCNP over-expression decreased apoptosis through up-regulating the expression levels of phospho (p)-signal transducers and activators of transcription (STAT) 3 and p-STAT5 in lung adenocarcinoma cells, whereas PCNP knockdown showed opposite trends. PCNP overexpression enhanced autophagy by increasing the expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) in lung adenocarcinoma cells, however an opposite trend was observed in the sh-PCNP group. In addition, overexpression of PCNP showed the tumor-promoting effect on xenografted lung adenocarcinoma, while PCNP knockdown reduced the growth of lung adenocarcinoma via regulating angiogenesis. Our study elucidates that PCNP can regulate the procession of human lung adenocarcinoma cells via STAT3/5 and PI3K/Akt/mTOR signaling pathways. PCNP may be considered as a promising biomarker for the diagnosis and prognosis in patients with lung adenocarcinoma. Furthermore, PCNP can be a novel therapeutic target and potent PCNP inhibitors can be designed and developed in the treatment of lung adenocarcinoma.

Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex, but not in the myocardium.

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease. Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system. However, it is unknown whether the protein kinase C ε (PKCε)-aldehyde dehydrogenase 2 (ALDH2) pathway is altered under chronic stress, and this study sought to address this question. A rat model of depression was established using a chronic unpredictable mild stress (CUMS) protocol. After experiencing CUMS for 4 weeks, the sucrose preference test and the forced swim test verified depressive-like behaviors. Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex, but was not altered in the myocardium. Western blot assays demonstrated reduced levels of ALDH2 and PKCε, but increased levels of 4-hydroxy-2-nonenal (4HNE) adducts. Caspase-3 expression did not obviously alter, but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex. In the myocardium, expression of ALDH2, PKCε and 4HNE adducts did not remarkably alter; while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated. Pearson's correlation test demonstrated that expression of 4HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex, but not in the myocardium. In conclusion, chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex, but not in the myocardium. Moreover, 4HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

Hydrogen Sulfide Alleviates Lipopolysaccharide-Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF-κB Signaling Pathways.

Diaphragm dysfunction is an important clinical problem worldwide. Hydrogen sulfide (H2S) is involved in many physiological and pathological processes in mammals. However, the effect and mechanism of H2S in diaphragm dysfunction have not been fully elucidated. In this study, we detected that the level of H2S was decreased in lipopolysaccharide- (LPS-) treated L6 cells. Treatment with H2S increased the proliferation and viability of LPS-treated L6 cells. We found that H2S decreased reactive oxygen species- (ROS-) induced apoptosis through the mitogen-activated protein kinase (MAPK) signaling pathway in LPS-treated L6 cells. Administration of H2S alleviated LPS-induced inflammation by mediating the toll-like receptor-4 (TLR-4)/nuclear factor-kappa B (NF-κB) signaling pathway in L6 cells. Furthermore, H2S improved diaphragmatic function and structure through the reduction of inflammation and apoptosis in the diaphragm of septic rats. In conclusion, these findings indicate that H2S ameliorates LPS-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-κB signaling pathways. Novel slow-releasing H2S donors can be designed and applied for the treatment of diaphragm dysfunction.

A case of acute thallotoxicosis successfully treated with double-filtration plasmapheresis.

The authors report a 48-year-old Chinese woman who presented with acute peripheral neuritis with progressive alopecia. Laboratory examinations disclosed a high blood concentration of thallium (97 microg/L) versus a normal value (0.9 microg/L), and she was diagnosed as having acute thallotoxicosis. After her hospitalization, the cutantest of dimercaptopropansulfonate sodium was positive and the patient refused to take Prussian blue because it caused constipation. She rapidly entered remission after assistance via double-filtration plasmapheresis (DFPP), suggesting the potential efficacy of DFPP for thallotoxicosis.

Adenovirus-vectored shRNAs targeted to the highly conserved regions of VP1 and 2B in tandem inhibits replication of foot-and-mouth disease virus both in vitro and in vivo.

Foot-and-mouth disease is a highly contagious and economically important disease of cloven-hoofed animals. RNA interference (RNAi) can be used as a rapid and specific antiviral approach. It was shown that treatment with recombinant adenovirus (Ad(VP1-2B)) carrying shRNAs targeted to the VP1 and 2B genes of FMDV expressed in tandem had marked antiviral effects against FMDV both in IBRS-2 cells and guinea pigs. Treatment with Ad(VP1-2B) both before and after FMDV infection was most effective in IBRS-2 cells, as the FMDV RNA transcripts could not be detected within 48 h post-challenge (hpc), and the viral RNA copy number at 72 hpc was only 0.02% of that in the positive control group. Delivery of Ad(VP1-2B) reduced significantly the susceptibility of guinea pigs to FMDV infection. All guinea pigs were protected within 3 days post challenge (dpc) when they were injected twice with the same dose of Ad(VP1-2B), and a third treatment with the same dose of Ad(VP1-2B) at 3 dpc was necessary to confer longer lasting protection (up to 6 dpc). In conclusion, application of such a adenovirus vector to inhibit more than one viral gene may be an advantageous method for prevention and therapy of FMDV infection.