Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

<p>Abstract</p> <p>Background</p> <p>Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H₂O₂)-induced cytotoxicity in a normal human hepatocyte cell line, HL7702.</p> <p>Methods</p> <p>We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH) release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS) levels, activities and protein expressions of superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) formation. Expressions of peroxisome proliferator-activated receptor (PPAR)-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test.</p> <p>Results</p> <p>The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H₂O₂. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1) and acyl-CoA oxidase (ACOX) induced by H₂O₂can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886.</p> <p>Conclusions</p> <p>Taken together, our findings suggest that L-carnitine could protect HL7702 cells against oxidative stress through the antioxidative effect and the regulation of PPAR-alpha also play an important part in the protective effect.</p

Expressions of IGFBP-5, cFLIP in cervical intraepithelial neoplasia, cervical carcinoma and their clinical significances: a molecular pathology

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor binding protein (IGFBPs) have been as potential tumor suppressors in the occurrence and development of tumors. Cellular Fas-associated death domain-like interleukin-1β-converting enzyme (FLICE)-like inhibitory protein (cFLIP) contains a death effect domain (DED), which blocks death receptor pathway and inhibits apoptosis.</p> <p>Methods</p> <p>We collected normal cervical tissues from 28 subjects, CIN samples from 37 patients, and cervical cancer tissues from 40 patients. In these samples, we then measured the expression levels of IGFBP-5 and cFLIP via RT-PCR and immunohistochemistry, and we detected the presence of high-risk HPV by Hybrid capture II assays in cervical secretions provided by the subjects.</p> <p>Results</p> <p>significant differences in the expression of IGFBP-5 protein among the normal, CIN, and CC tissues (P < 0.05). The highest expression of IGFBP-5 protein was found in CIN stage II and III tissues, whereas the expression of IGFBP-5 in CC samples was decreased relative to controls. The expression level was affected by factors such as clinical stage, pathological differentiation, and lymph node metastasis. Relative to the controls, IGFBP-5 mRNA content was higher in the CC group and lower in the CIN group (P < 0.05). No expression of cFLIP protein or mRNA was detected in normal cervical tissues. However, the degree of pathological changes correlated with increasing expression of cFLIP protein and mRNA, and significant differences were therefore detected between groups (P < 0.05). The HPV infection rates in the CIN and CC groups were much higher than in the normal group (P < 0.05).</p> <p>Conclusion</p> <p>IGFBP-5 expression is up-regulated in response to progression of CIN and down-regulated in invasive cervical carcinoma. Detection of IGFBP-5 and cFLIP expression levels, may prove particularly useful for diagnosing and differentiating CIN and CC.</p

1-Diphenyl­methyl-4-ethyl­piperazine-1,4-diium dichloride

In the title compound, C19H26N2 2+·2Cl−, the piperazinediium ring exhibits a chair conformation. The dihedral angle between the two benzene ring planes is 76.45 (13)°. Both amine-group H atoms participate in hydrogen bonding with the two Cl atoms

Microfluidic mass production of stabilized and stealthy liquid metal nanoparticles

Functional nanoparticles comprised of liquid metals, such as eutectic gallium indium (EGaIn) and Galinstan, present exciting opportunities in the fields of flexible electronics, sensors, catalysts, and drug delivery systems. Methods used currently for producing liquid metal nanoparticles have significant disadvantages as they rely on both bulky and expensive high-power sonication probe systems, and also generally require the use of small molecules bearing thiol groups to stabilize the nanoparticles. Herein, we describe an innovative microfluidics-enabled platform as an inexpensive, easily accessible method for the on-chip mass production of EGaIn nanoparticles with tunable size distributions in an aqueous medium. We also report a novel nanoparticle-stabilization approach using brushed polyethylene glycol chains with trithiocarbonate end-groups negating the requirements for thiol additives whilst imparting a ‘stealth’ surface layer. Furthermore, we demonstrate a surface modification of the nanoparticles using galvanic replacement, and conjugation with antibodies. We envision that the demonstrated microfluidic technique can be used as an economic and versatile platform for the rapid production of liquid metal-based nanoparticles for a range of biomedical applications.

Investigation of the morbidity of dry eye among special crowd in Shunde district

AIM: To investigate the morbidity of dry eye in policeman of Shunde district, and to analyze the related factors and proposed methods of preventing and treating dry eye.<p>METHODS:Totally 650 policemen who came for physical examination in Shunde district recived questionnaire survey. The patients with dye eye disease were finally diagnosed through slit lamp examination, Schirmer test, tear film break-up time(BUT)measurement and keratoconjunctival fluorescent staining. The morbidity among different policemen was further analyzed and stasticed.<p>RESULTS:The results showed that 152 in 650 policemen suffered from dry eye disease, the ratio was 23.4%. Comparied with security police and crimanl police, the ratio in traffic police, patrolman,and back office police was significantly higher. The prevalence was higher when the ages were greater than 40.<p>CONCLUSION: Unsuitable working environment, air contamination are high risk factors of dry eye disease

The Ginger-shaped Asteroid 4179 Toutatis: New Observations from a Successful Flyby of Chang'e-2

On 13 December 2012, Chang'e-2 conducted a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 $\pm$ 120 meters from the asteroid's surface. The highest-resolution image, with a resolution of better than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at the big end, a sharply perpendicular silhouette near the neck region, and direct evidence of boulders and regolith, which suggests that Toutatis may bear a rubble-pile structure. Toutatis' maximum physical length and width are (4.75 $\times$ 1.95 km) $\pm$10$\%$, respectively, and the direction of the +$z$ axis is estimated to be (250$\pm$5$^\circ$, 63$\pm$5$^\circ$) with respect to the J2000 ecliptic coordinate system. The bifurcated configuration is indicative of a contact binary origin for Toutatis, which is composed of two lobes (head and body). Chang'e-2 observations have significantly improved our understanding of the characteristics, formation, and evolution of asteroids in general.Comment: 21 pages, 3 figures, 1 tabl

Transcriptome Sequencing Investigated the Tumor-Related Factors Changes After T. gondii Infection

Toxoplasma gondii is an intracellular parasite and causes a global epidemic parasitic disease. T. gondii-infection could inhibit the growth of tumor. In this study, the transcriptomes of samples were detected by deep sequencing analysis. The transcriptome data was compared with reference genome to perform sequence alignment and the further analysis. The analyses of differential expression and the differentially expressed genes were performed in the present study. Genes involved in P53 signaling pathway, COLORECTAL cancer pathway, NON-SMALL CELL LUNG cancer signaling pathway, and BREAST cancer signaling pathway were up-regulated or down-regulated among the samples. The KEGG analysis indicated that the cancer pathways changed after infection of T. gondii. Furthermore, tumor-related mRNAs from different samples had a large difference, which suggested that the difference might provide important information in resisting cancer. The protein results indicated that tumor-related protein changes occurred after infection of T. gondii. In conclusion, the infection changed the cancer pathways, which could possibly inhibit the growth of tumor

Quality of and Recommendations for Relevant Clinical Practice Guidelines for COVID-19 Management: A Systematic Review and Critical Appraisal

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations.Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software.Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00–84.72) vs. 58.33% (52.78–68.06) in scope and purpose, 59.72% (38.89–75.00) vs. 36.11% (33.33–36.11) in stakeholder involvement, 64.58% (32.29–71.88) vs. 22.92% (16.67–26.56) in rigor of development, 75.00% (52.78–86.81) vs. 52.78% (50.00–63.89) in clarity of presentation, 40.63% (22.40–62.50) vs. 20.83% (13.54–25.00) in applicability, and 58.33% (50.00–100.00) vs. 50.00% (50.00–77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P &lt; 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/– azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued.Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/– azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this