ART1 promotes starvation-induced autophagy: a possible protective role in the development of colon carcinoma.

Autophagy plays a protective role in colorectal carcinoma. Arginine ADP-ribosyltransferase 1 (ART1) is an important mono-ADP-ribose transferase, which has been shown to play a role in biological processes such as proliferation and invasion of cancer cells. Interestingly, the role of ART1 in the regulation of autophagy is still not clear. We examined effects of overexpression or knockdown of ART1 by lentiviral transfection on starvation-induced autophagy of colon carcinoma CT26 cell lines in vivo and in vitro. The formation of autophagosome was detected by electron microscopy, acridine orange staining and expression of LC3 B. The molecular contributions of ART1 in regulation of autophagy were detected by western blotting or by co-immunoprecipitation. Additionally, inhibitors were used to study further the signaling pathway of ART1 in the regulation of autophagy. CCK8 assay, plate cloning assay, soft agar assay, examination of subcutaneous transplanted carcinoma in BALB/c mice, flow cytometry and Hoechst33342 staining were used to assess survival and apoptotic ability when starvation-induced autophagy modulated by ART1 was inhibited by 3-MA. Overexpression of ART1 promoted starvation-induced autophagy, which related to increases in the expression of Rac1, NF-κB, PARP-1, LKB1 and p-AMPK and a decrease in the expression of p-P70S6K. Correspondingly, knockdown of ART1 caused the opposite effects. ART1 also interacted with integrin α7. Additionally, changes of protein expressions were further validated following inhibition of Rac1 and PARP-1 in the starvation-induced ART1-GFP CT26 cells. Inhibition of ART1-stimulated starvation-induced autophagy restrained the growth and promoted apoptosis. ART1 is thus relevant in starvation-induced autophagy in colorectal carcinoma and may play essential roles in therapeutic anticancer strategies

Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae

Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Nimbolide Induces ROS-Regulated Apoptosis and Inhibits Cell Migration in Osteosarcoma

Osteosarcoma (OS) is a primary malignant tumor of bone and is most prevalent in children and adolescents. OS is frequently associated with pulmonary metastasis, which is the main cause of OS-related mortality. OS has a poor prognosis and is often unresponsive to conventional chemotherapy. In this study, we determined that Nimbolide, a novel anti-cancer therapy, acts by modulating multiple mechanisms in osteosarcoma cells. Nimbolide induces apoptosis by increasing endoplasmic reticulum (ER) stress, mitochondrial dysfunction, accumulation of reactive oxygen species (ROS), and finally, caspase activation. We also determined that Nimbolide inhibits cell migration, which is crucial for metastasis, by reducing the expression of integrin αvβ5. In addition, our results demonstrate that integrin αvβ5 expression is modulated by the PI3K/Akt and NF-κB signaling cascade. Nimbolide has potential as an anti-tumor drug given its multifunctional effects in OS. Collectively, these results help us to understand the mechanisms of action of Nimbolide and will aid in the development of effective therapies for OS

Synthesis and Physical Properties of Non-Crystalline Nylon 6 Containing Dimer Acid

In this study, a long carbon chain dimer acid is introduced into a nylon 6 structure and is copolymerized with different structural amines to produce amorphous nylon 6 by 4,4′-methylenebis(2-methylcyclohexylamine) (MMCA) in different copolymerization ratios. The effect of different structures and copolymerization ratios on the properties of nylon 6 is determined, along with the thermal properties, crystallinity, water absorption, dynamic mechanical properties, and optical properties. It is found that the melting point and the thermal cracking temperature Td10 of nylon 6 are respectively between 176 °C and 213 °C and 378 °C to 405 °C. The effect of introducing a bicyclohexane group containing a methyl side chain is greater than that of a meta-benzene ring, so COMM (synthesized by Caprolactam (C), dimer oleic acid (OA), and 4,4′-Methylenebis(2-methylcyclohexylamine) (MMCA)) has the lowest melting point, enthalpy, and crystallinity. As the copolymerization ratio increases, its thermal properties decrease. 10% is the lowest crystallinity. The amine structure containing a bicycloalkyl group has lower water absorption and a 10% copolymerization ratio gives the lowest water absorption. It contains the bicycloalkyl group, COM (synthesized by Caprolactam (C), dimer oleic acid (OA) and 4,4′-Methylenebis(cyclohexylamine) (MCA)), which has the highest loss modulus. The lowest loss modulus is noted for a copolymerization ratio of 7% and the value of tan δ increases as the copolymerization ratio increases. The introduction of nylon 6 with the bicycloalkyl groups, COMM and COM, significantly increases transparency. As the copolymerization ratio increases, the transparency increases and the haze decreases. The best optical properties are achieved for 10% copolymerization

The influence of atrial fibrillation on the mortality of incident ESRD patients undergoing maintenance hemodialysis.

BACKGROUND:Atrial fibrillation (AF) is highly prevalent, occurring in 1%-2% of the adult population, increasing the risk of stroke, and resulting in considerable healthcare costs. While stroke is a major complication of AF, end-stage renal disease (ESRD) patients also have a high risk of stroke, suggesting that AF is a possible risk factor for mortality of ESRD patients. However, whether the existence of AF at the initiation of hemodialysis predicts higher mortality risk of incident ESRD patients remains to be defined. METHODS:This retrospective cohort study was performed at Wanfang Hospital from January 2004 to May 2018. The end points were mortality of patients or the end of the study. Incident ESRD patients who were on maintenance hemodialysis for more than 3 months were eligible for inclusion. Cox proportional regression and Kaplan-Meier survival curves were used to determine the association between predictors and mortality. The association between AF and echocardiographic parameters, causes of death were also investigated. RESULTS:Of the 393 incident ESRD patients at initiation of hemodialysis, 57 (14.5%) had AF and the median age was 71 years. Patients with AF were significantly older; showed significantly higher C-reactive protein levels, more heart failure, chronic obstructive pulmonary disease and mortality. Multivariate Cox regression showed that AF had a hazard ratio of 4.1 (95% confidence interval: 2.4-7.0) for mortality. Age-specific analysis showed that AF was significantly associated with mortality in all age groups. Echocardiography measurements including ejection fraction and left ventricular hypertrophy (LVH) were similar in AF and non-AF patients. Cause-specific analysis showed that AF significantly associated with overall cardiovascular death and death due to acute myocardial infarction/coronary artery disease and sepsis. CONCLUSIONS:AF at the initiation of hemodialysis predicts higher mortality risk of incident ESRD patients regardless of age. The systolic function and degree of LVH were similar in AF and non-AF patients. The association between AF and sepsis-related death suggested the role of systemic inflammation on the pathogenesis of AF

Microbial etiology of pneumonia in patients with decreased renal function.

BackgroundPatients with renal impairment have altered immunity, which might cause vulnerability to specific pathogens and worsen pneumonia-related outcomes. Nonetheless, the microbiological features of pneumonia in patients with decreased renal function remain unknown.MethodsTherefore, we conducted a retrospective cohort study enrolling adult patients hospitalized with pneumonia to assess this knowledge gap. The baseline estimated glomerular filtration rate (eGFR) and first sputum microbiology during hospitalization were used for statistical analyses.ResultsOverall, 1554 patients hospitalized with pneumonia (mean age, 76.1 ± 16.7) were included, and 162 patients had died at the end of hospitalization. The cutoff eGFR value predicting mortality was ConclusionsThese findings suggested the altered immunity and vulnerability to S. aureus infection in patients with decreased renal function, which may be the underlying cause of worse outcomes of pneumonia in this group of patients